Vasoconstricción cerebral fatal, presentación inusual de una enfermedad inusual / Fatal reversible cerebral vasoconstriction syndrome: An unusual presentation of a rare disease

Resumen | El síndrome de vasoconstricción cerebral reversible se produce por la constricción variable, segmentaria y multifocal, de las arterias cerebrales y, generalmente, es de curso benigno. Se describe el caso de una mujer de 49 años que consultó por cefalea, síntomas visuales y convulsiones; tres días después, presentaba áreas de vasoconstricción en, por lo menos, dos territorios vasculares y dos segmentos de las mismas arterias. Fue internada en la unidad de cuidados intensivos para controlarle la presión arterial y recibir tratamiento médico. Tuvo una evolución tórpida y, en el séptimo día de hospitalización, desarrolló edema cerebral maligno, tras lo cual ocurrió la muerte cerebral. Se inició entonces el plan de donación de órganos y, posteriormente, se practicó una autopsia guiada del cerebro. El estudio de patología descartó vasculitis y reveló áreas de hemorragia en la convexidad cerebral. Se discuten los aspectos más relevantes de los casos con evolución fulminante informados en la literatura científica. El síndrome de vasoconstricción cerebral reversible se asocia con resultados fatales cuando los pacientes tienen una deficiencia neurológica focal, la neuroimagen inicial muestra alteraciones y hay un deterioro clínico rápido. Es importante conocer los factores asociados con un mal pronóstico, y establecer estrategias tempranas de intervención y prevención.

Abstract | The reversible cerebral vasoconstriction syndrome is a variable, segmental, and multifocal constriction of brain arteries, usually with a benign course. We describe the case of a 49-year-old woman who presented with headaches, visual symptoms, and seizures. Three days after admission, vasoconstriction areas were found in at least two vascular territories in two segments of the same arteries. The patient was admitted to the intensive care unit where her blood pressure was monitored and she received medical treatment. Surprisingly, the patient presented an unpredicted evolution in developing malignant cerebral edema on the seventh day after admission. She then suffered brain death and was taken to organ donation. A guided nervous system necropsy was later performed. The pathology discarded vasculitis and exhibited hemorrhage areas in the cerebral convexity. Herein, we discuss the most relevant aspects of cases with fulminant evolution reported in the literature. The reversible cerebral vasoconstriction syndrome is usually associated with fatal outcomes when patients exhibit focalization, their first neuroimaging typically shows disturbances, and a rapid clinical deterioration occurs. It is crucial to identify factors linked to poor prognosis and set intervention strategies and early prevention.

Temperature gradients in domestic cats over seven-years-old: descriptive analysis / Avaliação descritiva dos gradientes de temperatura em felinos domésticos com mais de sete anos

The temperature gradients are dynamic and noninvasive monitoring techniques that provide information on peripheral blood flow and have been related to the prognosis of patients with circulatory shock. This study evaluated 47 elderly domestic cats' temperature gradients, and we measured central (rectal) and peripheral (palmar, plantar and medial region of the radio) temperatures. Values found in this study are compatible with studies in young felines and differ from dogs and humans. The mean gradients found were 7.5°C for the central-peripheral; 5.6°C for the peripheral-environmental; 2.7°C for the skin-diff; and 0°C for the member-diff and the variables age and gender do not seem to influence these measurements. To the authors' knowledge, there is no description of temperature gradients in elderly domestic cats, so this study pretends to clarify the vasoconstriction response in this group of animals.(AU)

Os gradientes de temperatura são técnicas de monitoração dinâmicas e não-invasivas que fornecem informações sobre o fluxo sanguíneo periférico, e têm sido relacionados ao prognóstico de paciente com choque circulatório. O presente estudo avaliou os gradientes de temperatura em 47 felinos domésticos idosos aferindo as temperaturas central (retal) e periférica (palmar, plantar e região medial do rádio). Os gradientes encontrados foram 7,5°C para o centro-periférico; 5,6°C para o periférico-ambiental; 2,7°C para o skin-diff; e 0°C para o member-diff. As variáveis idade e sexo não pareceram influenciar as mensurações. Não há, em conhecimento dos autores, descrição prévia dos gradientes de temperatura em felinos domésticos idosos, e por isso esse estudo pretende contribuir com o entendimento sobre a capacidade de resposta de vasoconstrição nesse grupo de animais.(AU)

El lado oculto de la hipoxemia / The dark side of hypoxemia

Acute respiratory distress syndrome (ARDS) is characterized by an increase in the intrapulmonary shunt (measured by the PaO2/FiO2 ratio) caused by bilateral alveolar-interstitial infiltrates which are not fully explained by fluid overload. However, there are some ARDS cases which present severe hypoxemia without clear lung infiltrates. An example of this, which has generated great controver- sy, is the infection caused by SARS-CoV-2. Understanding the pathophysiology of hypoxemia is absolutely crucial in order to establish the most appropriate therapeutic strategy for each patient. In the case of a severe hypoxemia (PaO/ FiO2 < 200 which represents a shunt greater than 30%) with a chest X-ray (or CT) without clear and extensive bilateral infiltrates, it is important to consider that the shunt can be caused due to vascular involvement. This shunt could be explained two ways: an increase in pulmonary vascular resistance (PVR), which generates a right-to-left shunt through the patent foramen ovale (PFO), or an alteration of the hypoxic pulmonary vasoconstriction reflex (HPV). The HPV reflex is activated in an attempt to redistribute the vascular flow to better ventilated areas. However, there are some situations (such as viral infections) that can alter this reflex and worsen the hypoxemia. The concomitant use of vasoactive drugs (such as inhaled nitric oxide) and vasopressors (such as dopa- mine or norepinephrine) has been proposed with the aim of reducing PVR and the flow through the PFO; or to redistribute the flow to better ventilated areas if an alteration of the RVP is suspected.

Un síndrome de distrés respiratorio agudo (SDRA) se caracteriza por un incremento del intrapulmonar (medido por el cociente PaO2/FiO2) causado por una afectación alveolo-intersticial bilateral no explicada por sobrecarga hídrica. Sin embargo, hay casos de SDRA que presentan una marcada hipoxemia sin claros infiltrados pulmonares. Un ejemplo de este caso, que ha generado gran controversia, es la infección por SARS-CoV-2. El entendimiento de la fisiopato- logía de la hipoxemia es absolutamente clave para establecer la estrategia terapéutica más adecuada en cada paciente. Ante una hipoxemia grave (PaO2/FiO2 < 200 que representa un superior al 30%) y con una radiografía de tórax (o con TAC) sin claros y extensos infiltrados bilaterales, el podría deberse a una afectación vascular. Esto podría explicarse por dos causas: un aumento de las resistencias vasculares pulmonares (RVP), que genera un derecha- izquierda a través del foramen oval permeable (FOP) o una alteración del reflejo de vasoconstricción pulmonar hipóxico (VPH). El reflejo de VPH se activa en un intento por redistribuir el flujo vascular hacia las zonas mejor ventiladas. Sin embargo, existen situaciones (como infecciones víricas) que pueden alterar dicho reflejo y agravar la hipoxemia. Se ha propuesto el uso concomitante de fármacos vasoactivos (como el óxido nítrico inhalado) y vasopresores (como do- pamina o noradrenalina) con el objetivo de disminuir las RVP y el flujo a través del FOP; o para redistribuir el flujo a zonas mejor ventiladas si se sospecha una alteración del RVP.

Vascular mechanisms of monodesmosidic triterpene saponins isolated from Passiflora quadrangularis L / Mecanismos vasculares de saponinas triterpénicas monodesmosídicas aisladas de Passiflora quadrangularis L

Background: Passiflora quadrangularis L. has antihypertensive and anxiolytic properties observed in experimental models. Objectives: The aim of this work was to establish the vascular effects exerted by two known monodesmosidic triterpene saponins, 3-O-ß-D-glucopyranosyloleanolic acid (Compound 1) (not previously described for this plant) and, 3-O-[ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl] oleanolic acid (Compound 2), isolated from the ethanolic extract of Passiflora quadrangularis L. leaves. Methods: The structural elucidation was achieved by Nuclear Magnetic Resonance (NMR) experiments and High-Resolution Mass Spectrometry (HRMS). Aortic rings from Wistar rats, previously stimulated with phenylephrine (PE, 1µM) and washed, were exposed to cumulatively concentrations of compound 1 and compound 2 (10 to 400 µM). Ethanolic extract from leaves of P. quadrangularis L. (10 to 320 µg/ mL) and clonidine (1nM to 100µM) were also used for comparison. Concentration response curves of compounds 1 and 2 were examined in presence and absence of: endothelium, the alpha-2 antagonist yohimbine (1 and 100 µM), the alpha non selective antagonist phentolamine (1µM), the alpha-1 antagonist prazosin (1µM) and the calcium channel blocker verapamil (10 and 100 µM). In addition, cumulatively response curve of acetylcholine (ACh, 10nM to 10µM) and sodium nitroprusside (SNP, 1nM to 100µM) were assayed in rings precontracted with compounds 1 and 2 (400 µM). Results: Compounds 1 and 2 elicited a vasoconstriction response in intact aorta rings in similar way (pEC50: 3.92±0.01 and 4.09±0.01, respectively), effect that did not change in denuded rings (pEC50: 3.90±0.01 and 4.11±0.01). The potency order (pEC50) of compounds 1 and 2 decreased according to the following: verapamil (3.53±0.01 and 3.90±0.02; p<0.05) < yohimbine (3.65±0.01 and 3.94±0.02; p<0.05) < prazosin (3.86±0.01 and 4.30±0.02) < phentolamine (4.05±0.02 and 4.05±0.01). SNP but not ACh, was able to decrease the vasopressor effect of compounds 1 and 2 (pIC50: 8.61±0.01 and 8.24 ± 0.15, respectively). Conclusions: Compounds 1 and 2 are key metabolites responsible for the ex vivo vasoconstrictor response induced by P. quadrangularis L. Activation of voltage-dependent calcium channels and/or α2-adrenergic receptors stimulation could be mechanisms implicated.

Antecedentes: Passiflora quadrangularis L. tiene propiedades antihipertensivas y ansiolíticas observadas en modelos animales. Objetivos: El objetivo de este trabajo fue establecer los efectos vasculares ejercidos por dos conocidas saponinas triterpénicas monodesmosídicas: el ácido 3-O-ß-D glucopiranosiloleanólico (Compuesto 1) (no descrito previamente para esta especie vegetal) y el ácido 3-O-[ß-D-glucopiranosil- (1→2)-ß-D-glucopiranosil]oleanólico (Compuesto 2), aisladas del extracto etanólico de las hojas de Passiflora quadrangularis L. Métodos: La elucidación estructural se llevó a cabo mediante experimentos de Resonancia Magnética Nuclear (NMR) y determinaciones de Espectrometría de Masas de Alta Resolución (HRMS). Los anillos aórticos de ratas Wistar, previamente estimulados con fenilefrina (PE, 1 µM) y lavados, fueron expuestos a concentraciones acumulativas del compuesto 1 y compuesto 2 (10 a 400 µM). El extracto etanólico de las hojas de P. quadrangularis L. (10 a 320 µg / ml) y clonidina (1 nM a 100 µM) se utilizaron para la comparación. Las curvas de concentración respuesta de los compuestos 1 y 2 se examinaron en presencia y ausencia de: endotelio, el antagonista alfa-2 yohimbina (1 y 100 µM), el antagonista alfa no selectivo fentolamina (1 µM), el antagonista alfa-1 prazosina (1 µM) y el bloqueador de canales de calcio verapamilo (10 y 100 µM). Además, la curva de concentraciones acumulativas de acetilcolina (ACh, 10 nM a 10 µM) y nitroprusiato de sodio (SNP, 1 nM a 100 µM) se ensayó en anillos pre-contraídos con los compuestos 1 y 2 (400 µM). Resultados: Los compuestos 1 y 2 provocaron una respuesta de vasoconstricción en los anillos de aorta intactos de manera similar (pEC50: 3.92 ± 0.01 y 4.09 ± 0.01, respectivamente), este efecto no cambió en los anillos denudados (pEC50: 3.90 ± 0.01 y 4.11 ± 0.01). El orden de potencia (pEC50) de los compuestos 1 y 2 disminuyó de la siguiente manera: verapamilo (3.53 ± 0.01 y 3.90 ± 0.02; p <0.05) < yohimbina (3.65 ± 0.01 y 3.94 ± 0.02; p <0.05) < prazosina (3.86 ± 0.01 y 4.30 ± 0.02)

Síndrome De Vasoconstricción Cerebral Reversible Secundario A Fármacos: Reporte De Caso / Reversible Cerebral Vasoconstriction Syndrome Secondary To Drugs: Case Report

Resumen Introducción: El síndrome de vasoconstricción cerebral reversible es una entidad clínica y radiológica caracterizada por cefalea en estallido recurrente y vasoconstricción segmental multifocal de las arterias cerebrales, acompañado o no de otros déficits neurológicos, el cual resuelve espontáneamente en uno a tres meses. Métodos: Se reporta el caso clínico de una paciente que fue diagnosticada de síndrome de vasoconstricción cerebral reversible secundario a fármacos vasoactivos. Se plantea una búsqueda bibliográfica y una puesta al día de las últimas actualizaciones en relación a esta patología. Conclusión: Al menos la mitad de los casos de este síndrome son secundarios, sobre todo postparto y/o por la exposición a sustancias vasoactivas tales como drogas ilícitas, simpaticomiméticos y serotoninérgicos. Es trascendental identificar este cuadro a fin de retirar los posibles agentes causales, o evitar las complicaciones potenciales

Introduction: Reversible cerebral vasoconstriction syndrome is a clinical-radiologic syndrome characterized by recurrent thunderclap headache, with or without other acute neurological symptoms, and diffuse segmental constriction of cerebral arteries that resolves spontaneously within 3 months. Methods: It is described a clinic case of a woman, who was diagnosed with reversible cerebral vasoconstriction syndrome. A literature search and an update of the latest updates regarding this disease was done. Conclusion: At least half of the cases of this syndrome are secondary, especially postpartum and/or exposure to vasoactive substances such as illicit drugs, sympathomimetics and serotonergic drugs. It is crucial to identify this disorder in order to remove possible causative agents, or avoid potential complications.

Reversible vasoconstriction syndrome Study and management proposal / Síndrome de vasoconstricción reversible Propuesta de estudio y manejo

Abstract Reversible vasoconstriction syndrome is a group of clinical-radiological alterations that are characterized by severe sudden-onset headaches and reversible multifocal narrowing of the cerebral arteries. Most patients do not present with focal neurological deficit, although it can be seen in a small group, associated with cerebral edema, stroke or seizures. It is considered to be a benign process that causes disability and death in a minority of patients. The term 'reversible vasoconstriction syndrome' has been proposed to unify a variety of clinical syndromes which are similar, but have different etiologies, and have originated various eponyms. The apparently low frequency of reversible vasoconstriction syndrome and the way it presents make it a diagnostic challenge in the emergency room, and it may go unnoticed without an adequate medical history. A case probably related to the use of isometeptene is presented. (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1213)

Resumen El síndrome de vasoconstricción reversible es un grupo de alteraciones clínico-radiológicas que se caracterizan por cefaleas intensas de inicio brusco y estrechamiento multifocal reversible de las arterias cerebrales. La mayoría de los pacientes no presentan déficit neurológico focal, aunque puede verse en un grupo reducido asociándose con edema cerebral, ataque cerebrovascular o convulsiones. Es considerado un proceso benigno, en pocos casos originan discapacidad y muerte en una minoría de pacientes. El término de síndrome de vasoconstricción reversible se ha propuesto para unificar a una variedad de síndromes clínicos similares, pero de etiología diferentes y han originados diversos epónimos. La aparente baja frecuencia del síndrome de vasoconstricción reversible y su forma de presentación hace que se convierta en un reto diagnóstico en los servicios de urgencias y puede pasar desapercibido si no se tiene una historia clínica adecuada. Presentamos un caso probablemente relacionado al uso de isometepteno. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1213)

Reversible cerebral vasoconstriction syndrome a rare cause of post-partum headache: an anesthetic overview / Síndrome de vasoconstrição cerebral reversível, uma causa rara de cefaleia pós-parto: visão da anestesia

Abstract Reversible cerebral vasoconstriction syndrome is a cerebrovascular disorder leading to multifocal arterial constriction and dilation. Reversible cerebral vasoconstriction syndrome is possibly caused by transient deregulation of cerebral vascular tone. We report a rare case of a patient with chief complain of postpartum headache, was later diagnosed as a case of reversible cerebral vasoconstriction syndrome. A young full term primigravida with good uterine contraction admitted to labour room. Later she complained of leaking per vagina and on examination meconium stained liquor was noted. Caesarean delivery under spinal anesthesia was done and intra-operative period was uneventful. Both mother and baby were normal and shifted to postoperative ward and nursery respectively. In postoperative ward, mother complained of severe headache after 1 h and later developed seizure. Midazolam was given intravenously and was intubated and transferred to critical care unit for further investigation and management. Non contrast computerised tomography scan of brain showed right occipital intracerebral as well as subarachnoid bleed. CT angiography showed right vertebral artery narrowing without any other vascular malformation. Patient was managed in critical care unit for 2 days and then extubated and shifted to high dependency ward after a day observation and discharged 3 days later after a full uneventful recovery.

Resumo A síndrome de vasoconstrição cerebral reversível é uma doença cerebrovascular que leva à constrição e dilatação arterial multifocal. A síndrome de vasoconstrição cerebral reversível é possivelmente causada pela desregulação transitória do tônus vascular cerebral. Relatamos um caso raro de uma paciente com queixa principal de cefaleia pós-parto, posteriormente diagnosticada como um caso de síndrome de vasoconstrição cerebral reversível. A jovem primigesta a termo apresentando boa contração uterina foi internada em sala de parto. Mais tarde, a parturiente queixou-se de perda de líquido pela vagina e, ao exame, líquido amniótico manchado foi observado. O parto cesariano sob raquianestesia foi realizado, e não houve intercorrência no período intraoperatório. Tanto a mãe quanto o bebê estavam normais e foram transferidos para a sala de recuperação pós-operatória e berçário, respectivamente. Na sala de recuperação, a mãe queixou-se de forte dor de cabeça após uma hora e depois desenvolveu convulsão. Midazolam foi administrado por via intravenosa, e a paciente foi intubada e transferida para uma unidade de terapia intensiva para posterior investigação e tratamento. A tomografia computadorizada sem contraste do cérebro mostrou hemorragia intracerebral occipital direita e subaracnoide. A angiotomografia mostrou estreitamento da artéria vertebral direita, sem qualquer outra malformação vascular. A paciente foi tratada em unidade de terapia intensiva por dois dias e, em seguida, foi extubada e transferida para a ala de alta dependência onde permaneceu um dia em observação, recebendo alta hospitalar três dias depois, após uma recuperação completa e sem intercorrências.

Reporte de casos de síndrome de dedo azul / Blue finger syndrome: Case reports

RESUMEN El síndrome de dedo azul (SDA) se caracteriza por la coloración violácea o azul de uno o más dedos, puede serla primera manifestación de múltiples enfermedades, tanto las que presentan alteraciones directamente en los dedos o ser la expresión de enfermedades sistémicas; los mecanismos fisiopatológicos más comunes son trombosis, embolia, vasoconstricción grave o afección del lecho vascular que puede ser inflamatoria o no inflamatoria. Describimos 5 casos de SDA, donde resaltamos la importancia del diagnóstico temprano y enfatizamos en el concepto de evaluación y abordaje como una urgencia médica, sin importar la causa, ya que su manejo y tratamiento inicial, más el intento de lograr un tratamiento dirigido a una etiología podría disminuir complicaciones irreversibles como la necrosis o amputación.

ABSTRACT Blue finger syndrome (BFS), usually noted by the violet or blue coloration of one or more fingers, may be the first manifestation of several diseases. These may present with alterations directly on the fingers or be the expression of systemic diseases. The most common pathophysiological causes are thrombosis, embolism, severe vasoconstriction, or vasculature involvement that may be inflammatory or non-inflammatory. A description is presented of 5 cases of BFS, where the emphasis is placed on the importance of early diagnosis. The concept of evaluation and approach as a medical emergency is also stressed, because depending on this, it could reduce irreversible complications, such as necrosis and/or amputation.

Vasodilatory efficacy and impact of papaverine on endothelium in radial artery predilatation for cabg surgery: in search for optimal concentration

Abstract Objective: The aim of this study was to compare the efficacy of two different papaverine concentrations (0.5 mg/ml and 2 mg/ml) for vasospasm prevention and their impact on endothelium integrity. Methods: We have studied distal segments of radial arteries obtained by no-touch technique from coronary artery bypass graft (CABG) patients (n=10). The vasodilatory effect of papaverine (concentrations of 0.5 mg/ml and 2 mg/ml) was assessed in vitro, in isometric tension studies using ex vivo myography (organ bath technique) and arterial rings precontracted with potassium chloride (KCl) and phenylephrine. The impact of papaverine on endothelial integrity was studied by measurement of the percentage of vessel's circumference revealing CD34 endothelial marker. Results: 2 mg/ml papaverine concentration showed stronger vasodilatatory effect than 0.5 mg/ml, but it caused significantly higher endothelial damage. Response to KCl was 7.35±3.33 mN for vessels protected with papaverine 0.5 mg/ml and 2.66±1.96 mN when papaverine in concentration of 2 mg/ml was used. The histological examination revealed a significant difference in the presence of undamaged endothelium between vessels incubated in papaverine 0.5 mg/ml (72.86±9.3%) and 2 mg/ml (50.23±13.42%), P=0.002. Conclusion: Papaverine 2 mg/ml caused the higher endothelial damage. Concentration of 0.5 mg/ml caused better preservation of the endothelial lining.

Reactividad vascular in vitro y estudio morfométrico de venas safenas utilizadas como bypass coronario: técnica "no-touch" versus convencional / In vitro vascular reactivity and morphometric study of saphenous veins graft used as coronary bypass: "no-touch" versus conventional technique

Resumen Introducción: Prolongar la permeabilidad de los injertos utilizados en bypass coronario es un desafío constante. Objetivo: Comparar anatomofuncionalmente venas safenas humanas (VSH) extraídas con técnica convencional (TC) vs técnica "no-touch" (NT). Material y Método: Estudio experimental. Se diseccionó VSH con TC y NT en el pabellón de cirugía cardiaca del Hospital Regional de Antofagasta. Las muestras de VSH fueron seccionadas en anillos de 3 mm y conservados en cámaras de órganos aislados con solución Ringer-Krebs. Para evaluar la vasomotilidad se administró norepinefrina (10-6M), papaverina (10-4M), acetilcolina (10-6M) y nitroprusiato de sodio (10-5M). Un segmento de las muestras fue fijado en formalina al 10%, procesado con técnica histológica y analizado bajo microscopía óptica. Las muestras fueron teñidas con hematoxilina-eosina, Verhoeff y orceína. El análisis estadístico fue realizado mediante el software Prism Graphad. Resultados: Reactividad vascular: La vasoconstricción inducida por noradrenalina fue significativamente superior en anillos del grupo NT vs TC (p < 0,0001). La vasodilatación producida por papaverina y acetilcolina fue superior en el grupo NT (p < 0,004) y (p < 0,0003), respectivamente. Estudio morfométrico: El grupo NT presentó túnica muscular (0,755 vs 0,680 mm), adventicia (0,5600 vs 0,4663 mm) y pared total (1,344 vs 0,962 mm) más gruesa que el grupo TC. No hubo diferencias significativas respecto el número de vasa vasorum. Conclusión: El grupo NT responde significativamente mejor a estímulos vasoconstrictores y vasodilatadores. Los resultados se asocian con las diferencias morfométricas.

Introduction: Prolonging of the grafts permeability used in coronary bypass is a constant challenge. Objective: To compare anatomical and functional human saphenous veins (VSH) extracted "No touch" (NT) technique vs conventional technique (TC). Materials and Methods: Experimental study. VSH dissected with CT and NT in the Regional Hospital of Antofagasta cardiac surgery ward. VSH samples were sectioned into 3 mm rings and preserved in isolated organs chambers with Krebs-Ringer solution. To evaluate the vasomotor activity, norepinephrine (10-6M), papaverine (10-4M), acetylcholine (10-6M) and sodium nitroprusside (10-5M) was administered. A segment of samples was fixed in 10% formalin, processed and histological analyzed under light microscopy technique with hematoxylin-eosin, Verhoeff and orceína. Statistical analysis was performed using the Prism software Graphad. Results: Vascular Reactivity: norepinephrine-induced vasoconstriction was significantly higher in the group rings NT vs TC (p < 0.0001). Vasodilation was higher with papaverine and acetylcholine in the NT group (p < 0.004) and (p < 0.0003), respectively. Morphometric study: The NT group presented muscularis (0.755 vs 0.680 mm), adventitious (0.5600 vs 0.4663 mm), and total wall (1.344 vs 0.962 mm) thicker than the TC group. No significant differences in vasa vasorum number identified. Conclusion: The NT group vasoconstrictor and vasodilator responds significantly better. Results correlate with morphometric differences.

Mecanismos regulatorios del tono vascular pulmonar neonatal: una perspectiva molecular / Regulatory mechanisms of neonatal pulmonary vascular tone: a molecular perspective

La adaptación al medio extrauterino incluye un aumento considerable de la PaO2, que induce especialmente cambios estructurales y vasoactivos en la circulación pulmonar, que llevarán a una circulación previamente pobremente irrigada, a recibir ∼100% del gasto cardíaco del recién nacido, permitiendo el normal intercambio gaseoso. La regulación local de la circulación arterial pulmonar neonatal basal, es mantenida por un delicado equilibrio entre agentes vasoconstrictores y vasodilatadores. Este equilibrio, permite mantener la circulación pulmonar como un territorio de gran flujo sanguíneo y baja resistencia. La acción de los vasoconstrictores permite la formación de las interacciones entre actina y la cadena liviana de la miosina, esta es inducida en la célula muscular lisa principalmente por dos vías: a) dependiente de calcio, que consiste en aumentar el calcio intracelular, facilitando finalmente la unión de actina y miosina, y b) independiente de calcio, la cual a través de consecutivas fosforilaciones logra sensibilizar a las proteínas involucradas promoviendo la unión de actina y miosina. Estas acciones son mediadas por agonistas generados principalmente en el endotelio pulmonar, como endotelina-1 y tromboxano, o por agonistas provenientes de otros tipos celulares como la serotonina. Los agentes vasodilatadores regulan la respuesta vasoconstrictora, principalmente inhibiendo la señalización que induce la vasocontricción independiente de calcio, a través de la activación de proteínas quinasas que inhibirán la función de la ROCK quinasa, uno de los últimos efectores de la vasocontricción antes de la formación de la unión de actina y miosina. Esta revisión describe estos mecanismos de primordial importancia en las primeras horas de nuestra vida como individuos independientes.

The extrauterine-milieu adaptation includes a considerable increase in PaO2, that specifically induces structural and vasoactive changes at pulmonary circulation. Such changes transform a poor irrigated circulation into a circulation that receive ∼100% of neonatal cardiac output, supporting the normal alveolar-capillary gas exchange. Local regulation of basal neonatal pulmonary circulation is maintaining by a delicate equilibrium between vasoconstrictor and vasodilator agents. This equilibrium, allows to maintain the pulmonary circulation as an hemodynamic system with a high blood flow and a low vascular resistance. Vasocontrictors action allows actin and light-chain myosin interaction. Two main pathways induced this effect in smooth muscle cell: a) a calcium dependent pathway, that increases intracellular calcium, facilitating actin - myosin binding, and b) the independent calcium pathway, which achieves through consecutive phosphorylation reactions sensitize the proteins involved, promoting the binding of actin and light-chain myosin. These actions are mediated by agonists produced mainly in the pulmonary endothelium, such as endothelin-1 and thromboxane, or by agonists from other cell types such as serotonin. Vasodilator agents regulate the vasoconstrictor response, mainly by inhibiting signals that induce calcium-independent vasoconstriction, through activation of protein kinases, which in turn will inhibit the function of ROCK kinase, one of the last effectors of vasoconstriction before formation of the actin and light-chain myosin binding. This review will focus on describing these mechanisms of primal importance in the first hours of our lives as independent individuals.

Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi) / Acetilcolina produz contrações mediadas pela via da ciclooxigenase em vasos arteriais da rã chileno (Calyptocephalella gayi)

Abstract Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.

Resumo Estudos feitos em peixes marinhos (I. conceptionis e G. laevifrons) têm demostrado que a indometacina bloqueia a contração arterial mediada por acetilcolina (ACh). O objetivo do presente estudo foi avaliar o efeito da via da ciclooxigenase na contração induzida por ACh em vasos arteriais da rã chilena Calyptocephalella gayi. Foram dissecadas regiões das artérias pulmonares (PA), dorsal (DA), mesentérica (MA) e ilíaca (IA) de seis espécimes adultos e realizados estudos de tensão isométrica utilizando curvas dose-resposta (CDR) de ACh (10-13 a 10-3 M) na presença de um antagonista muscarínico (atropina, 10-5 M) e um inibidor das ciclooxigenases (indometacina, 10-5 M). Todas as artérias evidenciaram uma resposta vasoconstritora mediada por ACh. Esta resposta vasoconstrictora foi suprimida na presença de atropina nas artérias DA, MA, IA e atenuada na PA. A indometacina suprimiu a vasoconstrição na artéria MA e atenuou a resposta nas artérias PA, DA e IA. Tal como os peixes marinhos, a C. gayi tem um padrão de vasoconstrição mediado por Ach que é regulado pelos receptores muscarínicos e pela ciclooxigenase. Estes resultados sugerem a conservação dos mecanismos vasoconstrictores mediados por ACh→COX em peixes e rãs.

Palidez peri orbitaria post aplicación de midriaticos en neonatos con hidrocefalia asociado a efectos sistémicos / Periorbital pallor post application of mydriatic in infants with hydrocephalus associated to systemic effects

Una adecuada dilatación pupilar es necesaria para evaluar a neonatos con riesgo de desarrollar enfermedades oftalmológicas. Sin embargo, este procedimiento no está libre de efectos adversos locales o sistémicos. La vasoconstricción local posterior a la aplicación de midriáticos es una de estas complicaciones, existiendo además descritos efectos secundarios sistémicos. OBJETIVO: Presentar complicaciones asociadas al uso de midriáticos en 2 recién nacidos sometidos a evaluación oftalmológica. CASO CLINICO 1: Recién nacido de término con diagnóstico prenatal de restricción de crecimiento intrauterino e hidrocefalia. Al 5º día de vida se solicitó evaluación oftalmológica por presencia de opacidades corneales. Al realizar el procedimiento se evidenció palidez periorbitaria, al igual que taquicardia e hipertensión arterial en las siguientes 2 horas post procedimiento. Estos efectos secundarios se resolvieron espontáneamente pocas horas después del procedimiento. CASI CLINICO 2: Neonato de pretérmino de 27 semanas de gestación con antecedentes de síndrome de dificultad respiratoria, ductus arterioso persistente, hemorragia intraventricular grado III e hidrocefalia severa. Se solicitó examen oftalmológico a los 28 días de vida por sospecha de retinopatía del prematuro. A los 10 minutos post administración de midriáticos se observó palidez periorbitaria bilateral sin deterioro de signos vitales, presentando 24 horas después intolerancia a la alimentación y distensión abdominal. Se descartó enterocolitis necrotizante. CONCLUSIÓN: Es necesario establecer protocolos clínicos en relación al uso de midriáticos para reducir efectos deletéreos en neonatos de alto riesgo, como son los prematuros y aquellos con hidrocefalia. Por lo tanto, la monitoría debería realizarse durante la evaluación.

Adequate pupil dilation is needed to evaluate some neonates at risk of developing illness during this stage. However, this procedure is not free of adverse effects, either local or systemic. One of these complications is the local vasoconstriction of the preterm baby’s skin following the application of mydriatic eye drops. OBJECTIVE: To describe secondary local and systemic complications of pharmacological pupil dilation in 2 newborns. CLINICAL CASE 1: Full term baby with diagnosis of low-birth weight and hydrocephalia. An ophtalmological evaluation was performed at 5 days of age due to the presence of corneal opacities. Peri ocular pallor was observed during the procedure, as well as tachycardia and hypertension 2 hours later, spontaneosly recovered. CASE 2: Preterm newborn, 27 weeks of gestational age. Neonatal respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage and hydrocephalia were diagnosed at birth. At 28 days of life an ophtalmological evaluation was performed. After 10 minutes of mydriatic drops administration to evaluate preterm retinopathy, peri ocular pallor was observed, with spontaneous resolution; however, 24 hours later, the patient showed abdominal distention and feeding intolerance. Necrotizing enterocolitis was discarded, and symptoms were spontaneosly recovered. CONCLUSION: The establishment of protocols in relation to the number of drops to apply for dilation is needed to reduce deleterious effects on high risk infants, such as premature babies and those with hydrocephalus. Therefore this monitoring practice should be performed during the evaluation.

A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats / Uma Única Sessão de Exercício Resistido Melhora a Função Endotelial Aórtica em Ratos Hipertensos

Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p < 0.05) when compared to those of controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05) when compared to control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05). Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

Resumo Fundamento: O exercício físico é uma importante ferramenta para o aprimoramento da função endotelial. Objetivo: Avaliar os efeitos do exercício dinâmico resistido agudo na função endotelial de ratos espontaneamente hipertensos (SHR). Métodos: Após 10 minutos de exercício, a aorta foi removida para avaliação da expressão de óxido nítrico sintase endotelial (eNOS), óxido nítrico sintase endotelial fosforilada (p-eNOS1177) e óxido nítrico sintase endotelial induzível (iNOS), e para a construção de curvas concentração-resposta de acetilcolina (ACT) e fenilefrina (FEN). O protocolo FEN foi também realizado com lesão endotelial e antes e depois da administração de N-nitro-L-arginina metil éster (L-NAME) e indometacina. A resposta máxima (Emax) e a sensibilidade (EC50) a esses fármacos foram avaliadas. Resultados: Houve aumento do relaxamento induzido por ACT nos anéis aórticos dos ratos exercitados (Ex) (Emax = -80 ± 4,6%; p < 0,05) quando comparado àquele dos controles (Ct) (Emax = -50 ± 6,8%). A Emax à FEN diminuiu após exercício (95 ± 7,9%; p < 0,05) quando comparada àquela dos controles (120 ± 4,2%). Tal resposta foi abolida após administração de L-NAME ou lesão endotelial. Na presença de indometacina, a reatividade dos anéis aórticos à FEN diminuiu nos dois grupos (EC50= Ex -5,9 ± 0,14 vs. Ct -6,6 ± 0,33 log µM; p < 0,05/ Emax = Ex 9,5 ± 2,9 vs. Ct 17 ± 6,2%; p < 0,05). O exercício não alterou a expressão de eNOS e de iNOS, mas aumentou o nível de p-eNOS. Conclusão: Uma única sessão de exercício resistido melhora a função endotelial em ratos hipertensos. Essa resposta parece ser mediada por elevação da produção de NO através de ativação de eNOS.

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Síndrome de vasoconstricción cerebral reversible: Presentación como hemorragia subaracnoidea de la convexidad / Reversible Cerebral Vasoconstriction: Subarachnoid Convexity Hemorrhage

Objetivo: El propósito de este estudio es describir las características clínicas, epidemiológicas e imaginológicas de 5 pacientes con diagnóstico de síndrome de vasoconstricción reversible. Métodos: Se hizo una evaluación retrospectiva de las historias clínicas de cinco pacientes con clínica e imágenes compatibles con síndrome de vasoconstricción cerebral reversible en un hospital de alta complejidad de la ciudad de Medellín. Resultados: Los cinco casos correspondían a mujeres con una edad promedio de 50 años. En un caso se identificó como posible agente causal el consumo de bebidas energizantes con alto contenido de taurina. Todos los pacientes se presentaron con hemorragia subaracnoidea en la convexidad y evolucionaron de forma favorable. Conclusión: El síndrome de vasoconstricción cerebral reversible debe ser uno de los diagnósticos diferenciales etiológicos de hemorragia subaracnoidea de la convexidad; se presenta predominantemente en mujeres entre la cuarta y sexta década de la vida y usualmente tiene un curso benigno.

Objective: The purpose of this study is to describe the clinical, epidemiological and imaging characteristics of 5 patients with a diagnosis of reversible vasoconstriction syndrome. Methods: A retrospective evaluation of the clinical records of 5 patients with clinical and imaging diagnosis of reversible cerebral vasoconstriction syndrome was carried out in a high complexity hospital in the city of Medellín. Results: The five cases were women with an average age of 50 years. In one case, the consumption of energy drinks with a high taurine content was identified as a possible causative agent. All cases presented with brain convexity subarachnoid haemorrhage. The clinical outcome was favorable. Conclusion: The reversible cerebral vasoconstriction syndrome should be included in the differential diagnosis of convexity subarachnoid haemorrhage. It occurs predominantly in women between the fourth and sixth decade of life and usually has a benign course.

Levobupivacaine induces vasodilatation, but not vasoconstriction, in rat mesenteric artery / Levobupivacaína induz vasodilatação, mas não vasoconstrição em artéria mesentérica de rato

Introduction: Levobupivacaine (LEVO) can replace analgesia because it exhibits low toxicity and causes minor vasoconstriction, enabling its use in patients in whom vasoconstrictors are contraindicated. Objective: We aimed to evaluate the effects of LEVO in isolated rat superior mesenteric artery by using the vascular reactivity technique and compare its effect to that of lidocaine. Material and method: Arterial rings were obtained from the mesenteric artery of male Wistar rats and kept in organ baths. For recording isometric contractions, each ring was suspended by cotton threads from a force transducer, which was connected to a data acquisition system. Result: Both lidocaine and LEVO did not show a vasoconstrictor effect on the basal tone of the arterial rings with functional endothelium. However, when the rings were pre-contracted with phenylephrine, both drugs were able to induce concentration-dependent vasodilatation. The vasodilator effect induced by LEVO did not change after removal of the endothelium, or with the addition of tetraethylammonium (1 mM), a non-selective K+ channel blocker. In the rings without functional endothelium, which were pre-contracted with depolarizing Tyrode's solution (KCl 80 mM), LEVO-induced vasodilatation was not significantly different from that observed in the rings pre-contracted with phenylephrine. Moreover, it did not show a significant additional vasodilator effect compared to the maximal vasodilator effect of nifedipine. Conclusion: This study demonstrated that LEVO produces a vasodilator effect in the rat superior mesenteric artery in an endothelium-independent manner. This effect seems to be mediated via Ca2+ channel blockade in the vascular smooth muscle cells.

Introdução: Levobupivacaína pode ser uma nova alternativa para analgesia por apresentar baixa toxicidade e vasoconstrição, permitindo sua utilização em pacientes que apresentam contra-indicação no uso de vasoconstritores. Objetivo: Avaliar os efeitos da levobupivacaína utilizando a técnica de reatividade vascular em artéria mesentérica isolada de rato e comparar este efeito à lidocaína. Material e método: Anéis foram obtidos da artéria mesentérica de ratos machos Wistar e foram mantidos em cubas. Para o registro das contrações isométricas, cada anel foi suspenso por linhas de algodão fixadas a um transdutor de força acoplado a um sistema de aquisição. Resultado: Tanto a lidocaína como a levobupivacaína não apresentaram efeito vasocontritor sobre o tônus basal em anéis com endotélio functional. No entanto, quando os anéis foram pré-contraídos com fenilefrina, ambas as drogas induziram um vasorrelaxamento concentração-dependente. O efeito vasorrelaxante causado pela levobupivacaína não foi diferente após a remoção do endotélio, ou com o tetraetilamônio (1mM), um bloqueador não seletivo dos canais para. K+. Em anéis sem endotélio funcional e pré-contraídos com solução despolarizante de Tyrode (KCl 80mM), o vasorelaxamento induzido pela levobupivacaína não foi significativamente diferente daquele observado em anéis pré-contraídos com fenilefrina e não apresentou um efeito adicional significativo sobre o relaxamento máximo da nifedipina. Conclusão: Este estudo demonstrou que a levobupivacaína produz efeito vasorrelaxante em artéria mesentérica de rato, que é endotélio independente. Este efeito parece envolver os bloqueadores de canais para Ca2+ em célula muscular vascular lisa.

Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries / Efeito Vasodilatador Independente do Endotélio Induzido pela Jabuticaba (M. cauliflora) em Artérias Isoladas

Abstract Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect.

Resumo Fundamentos: Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. Objetivos: Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. Métodos: Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. Resultados: Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina também foi prejudicada pelo tratamento prévio com EHJ. A inibição da Ca2+ATPase do reticulo sarcoplasmático não alterou o relaxamento pelo EHJ. Além disso, o EHJ inibiu a contração causada pelo influxo de Ca2+ estimulado por fenilefrina e KCl (75 mM). Conclusão: O EHJ induz vasodilatação independente do endotélio. Ativação dos canais de K+ e inibição do influxo de Ca2+ através da membrana estão envolvidas no efeito relaxante do EHJ.

Avaliação dos efeitos vasculares e expressão de mRNA de receptores de drogas vasoconstritoras em leito arterial mesentérico de ratos normotensos, diabéticos, hipertensos renais um-rim, um clip (1R-1C) e 1R-1C diabéticos / Vascular reactivity and vasoconstrictor drugs receptors RNAmexpression on mesenteric artery bed of normotensive, diabetic, 1K-1C hypertensive and 1K-1C hypertensive-diabetic rats

O presente trabalho teve como objetivo avaliar e comparar a reatividade vascular de agentes vasoconstritores presentes nas soluções anestésicas locais (Adrenalina - vasoconstrição e vasodilatação; Felipressina - vasoconstrição), nas doses de 80, 160, 320, 640 e 1280ng (adrenalina) ou 0,25; 0,5; 1; 2 e 4 x10-3UI (felipressina), em leito arterial mesentérico deratos normotensos, diabéticos, hipertensos renais um-rim, um-clip (1R-1C) e hipertensos1R-1C-diabéticos. E correlacionar tal reatividadecom expressão de RNAm dos receptores 1A e 2- adrenérgicos, V1A para vasopressina e AT1A, AT1Be AT2 para angiotensina II visando verificar se a hipertensão arterial e o diabetes mellitus provocam alteração em modelo indutivo e isogênico. Ratos Wistar pesando 110-160g, foram anestesiados com mistura de quetamina e xilazina (50+10mg/ml/kg de peso), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Após 14 dias, receberam injeção subcutânea de estreptozotocina (50 e 60mg/kg de peso) para indução do diabetes mellitus sendo a glicemia testada pela veia caudal previamente aos experimentos (diabéticos). Após 30-42 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantou-se cânula de polietileno (PE-50) na artéria carótida esquerda para registro direto da pressão arterial. Após registro da pressão os animais tiveram a artéria principal mesentérica exposta e canulada. O leito arterial mesentérico foi então isolado e colocado em banho com solução nutritiva de Krebs a 37ºC. O cateter foi conectado ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro ®). Analisaram-se: a pressão máxima (vasoconstrição) e mínima (vasodilatação), o tempo necessário para atingir esse valor, duração total da resposta, integral e integral sobre a linha de base. Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak (distribuição normal) ou de Mann-Whitney (nãoparamétrico), quando apropriado, nível de significância de 5%. Todas as respostas máximas de vasoconstrição apresentaram comportamento dose-dependente, contudo, para os quatro grupos estudados, a resposta vasoconstritora para adrenalina foi significativamente superior à felipressina (p<0,05). Diabetes e hipertensão reduziram a resposta vasoconstritora da adrenalina e da felipressina, valores de integral sobre a linha de base, respectivamente para grupo controle, diabético, hipertenso e hipertenso-diabético: 2462±465; 1511±236; 2542± 5456 e 3749±819mmHg.s (p<0,05) para adrenalina e 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0,05) para felipressina. Tanto o diabetes quanto a hipertensão, associadas ou não, aumentaram significativamente o tempo para atingir a pressão máxima de vasoconstrição e a duração (p<0,05). As artérias mesentéricas de ratos diabéticos, hipertensos e diabéticos-hipertensos apresentaram expressão significativamente aumentada dos receptores 1Aadrenérgico, AT1B e AT2 para angiotensina II (p<0,05), enquanto receptor AT1A estava com a expressão aumentada apenas nos grupos diabéticos. A expressão do receptor 1A-adrenérgico é discrepante com os achados funcionais, o que pode ser justificado pela fase crônica da doença em que a PCR foi realizada. É possível correlacionar os dados obtidos com a menor atividade vasoconstritora da felipressina observada clinicamente. A maior sensibilidade às moléculas vasoconstritoras pode explicar a maior tendência de pacientes diabéticos desenvolverem hipertensão. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em pacientes hipertensos e diabéticos, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.(AU)

The main goal of this study wasto evaluate and compare vasoconstrictor agents present in local anesthetic solutions (Epinephrine - vasoconstriction and vasodilation, Felypressin - vasoconstriction) vascular reactivity on mesenteric artery bed of normotensive, diabetic, renal hypertensive one-kidney-one-clip (1K1C) and hypertensive 1K1C diabetic rats. Dosagesstudied were 80, 160, 320, 640 and 1280ng (epinephrine) or 0,25; 0,5;1; 2 and 4 x 10-3UI (felypressin). Also, we aimed to correlate artery response with RNAm expression of 1A and 2-adrenoceptors, V1A vasopressin receptor and AT1A, AT1B e AT2 angiotensin receptors, in order to verify if arterial hypertension and diabetes can lead to alterations on a inductive and isogenic model. Wistar male rats weighing 110-160g were anaesthetized with a mixture of ketamine and xylazine (50+10mg/ml/kg), had their abdominal cavity opened and a silver clipwith 0.25-mm gap was implanted in the main left kidney artery, the right kidney was surgically removed (1K1C-rats). After 14 days, they received a subcutaneous injection of streptozotocin (50 and 60 mg/ml/kg) for inducing diabetes, whereas the glycemia was tested via the tail vein prior to surgery (diabetic rats). Around 30-42 after the clip was implanted, all the groups were anaesthetized again and a polyethylene (PE-50) cannula was implanted on the left carotid artery for direct arterial pressure register. After registering the pressure, the animals had their main mesenteric artery exposed and cannulated. The mesenteric artery bed was then isolated and transferred to a bath with Krebs nutritive solution at 37ºC. The catheter was connected to the computer register system (PowerLab®) using a specific software (Chart 5Pro ®). The following parameters were analyzed: maximum (vasoconstriction) and minimal pressure (vasodilating), the amount of time necessary to achieve this number, total duration of the reaction, integral and integral over baseline. The data was submitted to analysis of variance of repeated measures (ANOVA), followed by a Holm-Sidak (normal distribution) test or Mann Whitney (parametrics) test when suitable, with a significance level of 5%. All maximum vasoconstriction results presented dosage-dependant behavior, however, for the four groups tested, the vasoconstrictive result for epinephrine was significantly superior to felypressin (p<0,05). Diabetes and hypertension significantly reducedepinephrine and felypressin vasoconstrictor responses, integral above baseline, respectively, for control, diabetic, hypertensive and hypertensive-diabetic groups:2462±465; 1511±236; 2542± 5456 e 3749±819 mmHg.s (p<0.05, epinephrine) and 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0.05, felypressin). Both diabetes and hypertension, associated or not, significantly increased time necessary to achieve maximum vasoconstrictor response and its duration (p<0,05). Diabetic, hypertensive and hypertensive-diabetic mesenteric arteries presented 1A-adrenoceptor, AT1B and AT2 angiotensin II-receptor gene expression significantly increased when compared with control group (p<0,05), while AT1Areceptor presented this pattern only in diabetic groups.1A-adrenoceptor gene expression did not confirm functional data, probably due to chronic disease state in wich PCR was performed. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em ratos hipertensos e diabéticos não tratados, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.Its possible to correlate our datawith reducedvasoconstrictor activity of felypressinin clinical use. Increased sensibility and receptor population for vasoconstrictor endogenous molecules could explain diabetic populations tendency to develop arterial hypertension. Our results suggest that epinephrine is more potent than felypressin and both vasoconstrictors presents reduced effects on diabetic and hypertensive patients, what reinforces vasoconstrictor associated with local anesthetic use in this population.(AU)