[Effect of sulodexide on aortic vasodilation capacity and associated morphological changes in rats with streptozotocin-induced diabetes]. / Efecto del sulodexide sobre la capacidad de relajación y alteraciones estructurales de la arteria aorta en ratas diabéticas por estreptozotocina.

Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans (GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, i.v. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.

Cardiovascular excitatory effect on rats of a fraction isolated from the eyestalk of shrimp: Peneaus vanameii.

The crustacean nervous system is an important source of substances with diverse biological activities, particularly affecting invertebrate cardiocirculatory physiology. However, the effects of these substances on the cardiovascular system of higher vertebrates are not very well documented. The purpose of this study was to evaluate the effects of a cardioexcitatory substance (CES) isolated from the eyestalk of the shrimp Peneaus vanameii on rat cardiovascular function. The administration of a purified fraction of this substance raised mean arterial pressure by 37.33 +/- 5.00 mm Hg, pulse pressure 35.00 +/- 4.93 mm Hg and heart rate 80.00 +/- 12.83 beats/min over basal values (p < 0.01). Evaluation of the possible underlying mechanisms of this hypertensive and tachycardic effect reveled that dihydroergotamine pretreatment (20 microg/0.2 mL) reduced the effect of CES on mean blood pressure, but not on heart rate. Propranolol pretreatment (4 microg/0.2 mL) reduced the tachycardia, but not the hypertensive response. Enalapril pretreatment (5 microg/0.2 mL) did not modify the effects induced by CES on heart rate or blood pressure, and the verapamil pretreatment (1 microg/0.2 mL) reduced both cardiovascular changes by 85% (p < 0.01). These results indicate that CES isolated from the shrimp eyestalk produces hypertension and tachycardia mediated by adrenergic receptors in association to calcium channels activation.

[Decrease of affinity between arterial proteoglycans and LDL isolated from smokers and non-smokers with vitamin E and C administration]. / Disminución de la afinidad entre proteoglicanos arteriales y LDL aislada de fumadores y no fumadores por administración de vitaminas E y C.

LDL interaction with arterial proteoglycans and its oxidative modification is closely related to atherosclerosis. The objective of the present study was to examine the effect of the individual administration of vitamin E and a combination of vitamin E and C on LDL affinity for arterial proteoglycans in smokers and non-smokers subjects. Twenty smokers and ten non-smokers healthy subjects received by the oral route placebos of vitamins E and C for 15 days; then vitamin E (400 mg/d) for 30 days and finally vitamin E plus vitamin C (1000 mg/d) during the following 30 days. During the vitamin E supplementation period, the affinity of LDL for arterial proteoglycans decreased 19.3% in smokers and 25.2% in non-smokers. When the subjects received vitamin E plus vitamin C, the affinity of LDL for arterial proteoglycans decreased 25.6% and 30.1% in smokers and non-smokers respectively. In conclusion, simultaneous administration of vitamins E and C showed a synergistic effect to diminish the affinity of the LDL by arterial proteoglycans, that was greater than caused by the administration of vitamin E alone. These finding suggest a potential antiatherogenic effect of both antioxidant vitamins.

[Epicardial adipose tissue and its association to plasma adrenomedullin levels in patients with metabolic syndrome]. / Tejido adiposo epicárdico y su asociación con niveles plasmáticos de adrenomedulina en pacientes con síndrome metabólico.

OBJECTIVE: To assess the association between epicardial adipose tissue thickness (EAT) and plasma adrenomedullin plasma levels in patients with metabolic syndrome (MS). METHODS: Twenty-one patients (12 females and 9 males) with MS according to the International Diabetes Federation guidelines, aged 22-58 years, were enrolled into the study and compared to 19 age-matched control subjects without MS. Plasma glucose, lipid, and adrenomedullin levels were assessed. EAT, left ventricular mass, and carotid intima-media thickness were evaluated by transthoracic two-dimensional echocardiography. RESULTS: No statistically significant differences were found between the groups in age, sex, and height. Body weight, abdominal circumference (AC), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly higher (p=0.0001) in MS patients; this group also showed significantly higher glucose (p=0.001), total cholesterol (p=0.01), LDL-C (p=0.03), VLDL-C (p=0.005), triglyceride (p=0.002), Tg/HDL ratio (p=0.0001), and plasma adrenomedullin (3.49±1.21 vs 1.69±0.92 ng/mL; p=0.0001) levels and lower HDL-C (p=0.02) levels as compared to the control group. EAT was significantly thicker in MS patients compared to the control group (8.45±3.14 vs 5.43±0.96; p=0.0001), showed a positive correlation to BMI (r=0.347; p=0.02), AC (r=0.350; p=0.02), DBP (r=0.346; p=0.02), and adrenomedullin levels (r=0.741; p=0.0001). In multiple linear regression analysis, adrenomedullin was the only parameter associated to EAT (R(2)=0.550; p=0.0001). CONCLUSION: In this small patient group, a statistically significant association was found between EAT and plasma adrenomedullin levels, which may be considered as a potential biomarker of MS.

[Cardiovascular responses to hypertonic NaCI injection into the anteroventral third ventricle region in rats with fructose-induced hypertension and insulin resistance]. / Respuestas cardiovasculares al NaCI hipertónico inyectado en la región anteroventral del tercer ventrículo de ratas con hipertensión e insulinorresistencia inducidas por fructosa.

INTRODUCTION AND OBJECTIVES: To investigate the hemodynamic sympathetic response evoked by NaCI microinjection into the third ventricle anteroventral brain area (AV3V) in rats long-term fed with high fructose diet. METHODS: Twelve male rats received 60% fructose enriched diet for 6 months. Control rats (n=12) received regular diet. RESULTS: Fructose diet increased (P< .01) body weight; plasma glucose, triglycerides; cholesterol, insulin; systolic (SBP) and diastolic blood pressure (DBP). Basal heart rate (HR) did not change. AV3V microinjection of 2 microL of hypertonic 1.5 M NaCI in fructose fed rats increased SBP 44.64(3.6) mm Hg, DBP 19.9(2.4) mm Hg and HR 66.2(8.4) beats/min over basal values (P< .01). In control rats, smaller responses were observed, SBP increased 28.33(3.10) mm Hg, DBP 13.0(1.9) mm Hg and HR 23.0(5.0) beats/min over basal values (P< .01). CONCLUSIONS: Long-term fructose diet in rats induces cardiovascular hyperactivity of AV3V neurons to sodium chloride, and is associated to hypertension and insulin-resistance.

Adrenomedulina: ¿Más que una simple hormona?

La adrenomedulina es un péptido vasodilatador, presente en el sistema cardiovascular, riñón, pulmón, glándula adrenal y en el adipocito. Este péptido ha venido adquiriendo una importancia creciente en los últimos años, ya que se han descrito niveles elevados del mismo en patologías como el síndrome metabólico, diabetes mellitus tipo 2, hipertensión arterial y en aterosclerosis, lo cual pone de manifiesto su relevancia en la fisiopatología de estos trastornos y su posible uso como marcador de riesgo cardiometabólico. A nivel cardíaco, el efecto inotrópico positivo de este péptido parece estar mediado por un aumento del calcio citosólico, independiente de AMP cíclico; reduce la hipertrofia de los miocardiocitos y en la insuficiencia cardíaca los niveles plasmáticos de adrenomedulina están incrementados. La adrenomedulina tiene efecto vasodilatador sistémico y pulmonar y se encuentra incrementada en el plasma de sujetos con hipertensión arterial esencial y en hipertensos con hiperaldosteronismo primario. En riñón, la adrenomedulina induce efecto diurético y natriurético, aumento de la filtración glomerular y disminución de la reabsorción tubular distal de sodio; sus niveles están elevados en la insuficiencia renal crónica. La adrenomedulina está elevada en pacientes diabéticos con mal control metabólico, pero su papel patogénico en la enfermedad no está claro.

Adrenomedullin is a vasodilatory peptide found in the cardiovascular system, kidneys, lungs, adrenal glands and adipocytes. This peptide has been rising interest during the last years because increased plasma levels of it have been found in several pathological conditions such as the metabolic syndrome, type 2 diabetes mellitus, arterial hypertension and atherosclerosis, pointing to a possible physiopathologic role in these diseases and the potential use as a clinical cardiometabolic marker. In the heart, adrenomedullin has a positive inotropic action, probably mediated through cytosolic increase of calcium concentration, independent of cyclic AMP; it also can reduce cardiomyocites hypertrophy. In heart failure, adrenomedullin levels are increased and show systemic and pulmonar vasodilator effect; its plasma levels are increased in patients with essential arterial hypertension and hypertensives with primary hyperaldosteronism. In the kidneys, adrenomedullin is natriuretic and diuretic, it elevates glomerular filtration rate and reduce distal tubules sodium reabsorption; in patients with renal failure, adrenomedullin levels are increased. In diabetic patients, adrenomedullin plasma levels are increased; however, its pathogenic role in this disease is not yet clear.

Efecto del sulodexide sobre la capacidad de relajación y alteraciones estructurales de la arteria aorta en ratas diabéticas por estreptozotocina / Effect of sulodexide on aortic vasodilation capacity and associated morphological changes in rats with streptozotocin-induced diabetes

La disfunción endotelial (DE) se presenta en pacientes con hipercolesterolemia, hipertensión arterial, obesidad y diabetes mellitus. Evidencias sugieren un papel de los glicosaminoglicanos en la DE. Evaluamos el efecto del sulodexide (SLD), un glicosaminoglicano utilizado en el tratamiento de la albuminuria y la enfermedad isquémica en pacientes diabéticos, sobre la relajación arterial y los cambios morfológicos en un modelo experimental de diabetes tipo 1. La diabetes se indujo a ratas Sprague Dawley administrando estreptozotocina (STZ), 60 mg/kg, i.v. Los animales fueron distribuidos en los siguientes grupos: I= control, II= diabéticas, III: control + sulodexide, IV= diabéticas + sulodexide (15 mg/kg/día s.c). A los 3 meses fueron sacrificados, las aortas extraídas para evaluar la relajación vascular inducida por acetilcolina (Ach) y nitroprusiato de sodio en anillos precontraídos con fenilefrina. Fueron evaluadas histológicamente mediante microscopía de luz y coloraciones diversas. El SLD in vitro no modificó la tensión basal de los anillos arteriales en reposo o precontraídos con fenilefrina. La diabetes disminuyó la capacidad de relajación arterial en respuesta a la Ach en un 28,8-35,1% vs control, efecto que fue prevenido por SLD. No se observó diferencia significativa en la relajación inducida por nitroprusiato sódico entre los grupos. El estudio histológico en los animales diabéticos mostró alteraciones estructurales, particularmente en la íntima y la adventicia, cambios que fueron prevenidos por el tratamiento con SLD. Nuestros resultados apoyan la potencial utilidad terapéutica del SLD en el tratamiento de la disfunción endotelial.

Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans(GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, iv. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.

Testosterone and nandrolone sensitization of brain anteroventral area of third ventricle to hypertonic NaCl-induced sympathetic response.

Androgenic steroids increase atherogenesis, thrombogenicity and endothelial dysfunction when administered in high doses, however their effects on NaCl sensitivity of the brain anteroventral area of the third ventricle (DeltaV3V) have not been explored. Sprague-Dawley male rats were anesthetized with sodium pentobarbital (40 mg/kg) and the femoral intra-arterial blood pressure and heart rate monitored through a strain-gauge blood pressure transducer and tachograph. DeltaV3V microinjections of (2 microl) 1.5 mol/l NaCl solution were done according to brain coordinates: AP = 7.0 mm, L = 1.0 mm, D = 7.5 mm through a 0.2-mm diameter stainless steel needle. The injection site was verified with 1.0 microl neutral red solution. Basal systolic blood pressure increased 37.6 and 39.6 mm Hg after testosterone (1 mg/kg/day for 20 days) and nandrolone (1 mg/kg/day for 20 days) treatment respectively; diastolic blood pressure also increased upon testosterone and nandrolone treatment in 36.4 and 53.1 mm Hg, respectively; basal heart rate did not change. Vasopressor response to 1.5 mol/l NaCl DeltaV3V microinjection was higher in testosterone-treated rats; systolic blood pressure increased 56.0 vs. 28.3 control mm Hg; diastolic blood pressure increased 54.0 vs. 25 control mm Hg. This hypertensive response was 29% longer lasting in testosterone compared to vehicle-treated rats. The same pattern of DeltaV3V sensitization to hypertonic NaCl was observed in nandrolone-treated rats. Blood lipid profile changed to a proatherogenic fashion upon testosterone and nandrolone long-term treatment; the plasma-free testosterone concentration increased from 4.9 +/- 0.9 to 36.0 +/-7.1 pg/ml with the same testosterone treatment schedule. In conclusion, long-term androgenic steroid treatment sensitizes the brain DeltaV3V region to hypertonic NaCl which in turn conducts into a sympathetic vasopressor and heart rate-stimulating action.

[Synergistic antioxidative effect of vitamins E and C on low density lipoproteins from smokers and non-smokers subjects]. / Efecto sinergico antioxidante de las vitaminas E y C sobre la lipoproteina de baja densidad en fumadores y no fumadores.

LDL-lipids peroxidation is an important step in LDL atherogenicity. Tobacco smoke, promotes oxidative stress and reduces LDL-alfa tocoferol content and plasmatic vitamin C concentration. The objective of this double-blind randomized study was to assess the effect of vitamins E and C combined administration, on oxidative susceptibility of LDL isolated from 20 smokers and 10 non-smokers healthy volunteers who received placebo for 15 days and then concomitantly received 400 mg/d vitamin E and 1000 mg/d vitamin C for 30 days. At the end of placebo administration of and vitamins E and C combination; plasma total cholesterol, LDL-C and HDL-C values did not change significantly (p>0.05), plasma triglycerides increased significantly within a normal accepted range (p<0.05) and LDL oxidation susceptibility in smokers decreased by 41,3% and in non-smokers by 54,4% (p<0.05 vs placebo). In conclusion, simultaneous administration of vitamins E and C exerts an important antioxidant effect on LDL-lipids peroxidation. This effect could operate as an attenuating factor of the increased atherogenesis commonly observed in smoker subjects.

[Design of an impedance plethysmograph for reactive hyperemia evaluation in the forearm]. / Desarrollo de un pletismografo de impedancia para evaluar la hiperemia reactiva en el antebrazo.

Impedance pletismography is based on the evaluation of the voltage change that occur as a consequence of blood flow variations in a particular tissue section. Current applied for the procedure should be alternating, weak and of high frequency to avoid electrically excitable cells stimulation, such as muscles and nerves. Blood volume changes can be measured by this method and has been applied in the diagnosis of deep venous thrombosis of limbs. An impedance meter was designed and built to be used in the forearm of patients. It consists of a voltage stabilizer TPS 76150 with simultaneous ECG recording (DII lead). Injected signal had 50 KHz (Wien's bridge) and registered through two operational amplifiers LM 3080 (1 mA). Signal was demodulated and amplified. Electrodes used were made of silver strips with conductance improved by conductivity gel, fixed by elastic rubber strips. Circuit wiring and equisition software was developed at the Bioengineering Department of Simón Bolívar University. Fifteen healthy subjects, age range 18-30 years old, were submitted to noninvasive forearm blood flow evaluation with the already described electronic device. Brachial artery occlusions were made with a cuff at subdiastolic, supradiastolic and suprasystolic blood pressures, for 60 and 90 seconds and then this occlusion was abruptly released. The curve was displayed and recorded in a portable PC (laptop). During suprasystolic occlusion the impedance observed curve showed a progressive increased until stabilization. When occlusion was released a sudden peak appeared which corresponds to reactive hyperemia of the forearm. This peak has been associated to the secretion of endothelial vasodilatory substances. In conclusion, this device is suitable to be used in clinical settings for the evaluation of reactive hyperemia and potentially useful in diagnosis of deep veins occlusions.

El sistema cardiovascular

El síndrome metabólico tiene una fuerte asociación con la patogénesis de la diabetes tipo 2, la hipertensión arterial y las enfermedades cardiovasculares. Los niveles plasmáticos de adiponectina estás disminuidos en los pacientes con síndrome metabólico y diversos estudios demuestran que esta hormona ejerce efectos favorables sobre la aterogénesis, la función endotelial y el remodelado vascular. Esta revisión abordará los estudios tanto epidemiológicos como experimentales que sustentan los efectos pleiotrópicos de la adiponectina en el sistema cardiovascular.

The metabolic syndrome has a strong association with the pathogenesis of type 2 diabetes, arterial hypertension and other cardiovascular diseases. Adiponectin plasma levels are reduced in patients suffering the metabolic syndrome and in many basic and clinical studies have demonstrated that adiponectin improves endothelial function, vascular remodelling and atherogenesis. This review will consider the epidemiological and experimental findings bringing support to the pleiotropic effects adiponectin on the cardiovascular system.

Cocaine long-term administration induces myocardial depressant effects and adrenoceptors desensitization.

Cocaine as a drug of abuse can cause many cardiovascular toxic effects. The objective of this work was to study the mechanism of the negative inotropic effect of cocaine on isolated right ventricle strips and its relationship with myocardial catecholamines desensitization after long- term cocaine administration. Right ventricle strips were incubated in oxygenated Krebs solution at 37 degrees C, and driven with 2 ms, 15 mA, 1.8 Hz electric square pulses. Beat tension force was recorded with a force-displacement transducer. In control long-term saline (0.9% NaCl) treated rats (0.1 mL/Kg x 15 days, s.c.), in vitro 0.1-30 microM cocaine progressively increased the ventricle strip force up to 53% over baseline value. On the contrary, a negative inotropic effect of cocaine was observed in strips obtained from long-term cocaine treated rats (3 mg/Kg x 15 days, s.c.). The contractile force change ("Bowditch" phenomenon) induced by short (30s) rising of myocardial stimulating frequency to 2.7, 3.5 and 4.3 Hz respectively, was completely reversed in ventricular strips obtained from long-term cocaine treated rats. Myocardial desensitization to isoproterenol (saline 4.67 nM Vs cocaine 13.17 nM DE50) and to phenylephrine (saline 5.44 nM Vs cocaine 8.6 nM DE50) was observed in long term cocaine treated rats when compared to the control group. Aorta desensitization to phenylephrine-induced constriction in long-term cocaine treated rats was also observed; phenylephrine DE50 increased from 1.9 nmol/l in control rats to 15.5 nmol/l in long-term cocaine treated ones. Cocaine metabolites, benzoylecgonine and ecgonine methyl ester were excreted (121.6 micrograms/ml) in urine samples from all cocaine treated rats and not in the saline treated group. Long-term cocaine treatment seems to interfere with the cytosolic calcium increase that normally occurs during systole; this could explain its negative inotropic effect observed during in vitro cocaine reexposure. The adrenergic receptor desensitization induced by chronic cocaine administration could lead to a full expression of the negative inotropic effect of this drug. Extrapolated to clinical grounds, this mechanism could explain some clinical cases of heart failure reported in cocaine overdosed addicts.

Influencia de la administración a largo plazo de aceites de palma y maíz en la dieta sobre la vasoconstricción y vasodilatación arterial de la aorta del conejo / Influences of the long term administration of palm oils and corn in the dirt on the vasoconstrictor an arterial vasodilator of the aorta of the rabbit

Se evaluó el efecto de la administración en la dieta de aceite de palma o de maíz a largo plazo sobre los lípidos sanguíneos y la actividad arterial de anillos de aorta de conejo, agentes vasoconstrictores y vasodilatadores dependientes e independientes del endotelio. Los conejos albinos fueron divididos en tres grupos de 12 conejos cada uno, que recibieron: grupo I (control), dieta convencional de conejarina Grupo II, conejarina con aceite de palma (10 por ciento), Grupo III: conejarina con aceite de maíz (10 por ciento) por un período de 4 meses. Se tomaron muestras de sangre al inicio y al final del estudio, cuando fueron anestesiados, se extrajo la aorta y se cortó en anillos que fueron incubados en solución de Kerbs oxigenada para la evaluación de la reactividad a fenilefrina (FEN), acetilcolina (Ach) y niprotusiato de sodio (NPS). El aceite de palma aumentó el colesterol total plasmático de 20,4 a 35,1 mg/dL (p<0,05) y el de maíz de 27,0 a 44,5 mg/dL (p<0,05); el aceite de palma aumentó la HDLc de 12,2 a 24,0 mg/dL (p<0,015) y el aceite de maíz no modifico significativamente este parámetro, pero aumentó los triglicéridos de 21,5 a 46,0 mg/dL (p<0.004). La DE-50 de la curva dosis-respuesta (CDR) a la Ach en los anillos de la aorta control, fue 2,4 x 10 a la menos 7 mol/L y en el grupo que recibió aceite de palma, la CDR fue desplazada a la izquierda y la DE-50 disminuyó a 7,5 x 10 a la menos 8 mol/L (p<0,05); en el grupo que recibió aceite de maíz la De-50 disminuyó a 6,6 x 10 a la menos 8 mol/L (p<0,01). La reactividad a FEN en el grupo que recibió aceite de palma no cambió (p> 0,05) y desplazó significativamente la CDR a la derecha en los que recibieron aceite de maíz (p<0,05). La CDR al nitroprusiato de sodio no cambió en los conejos que recibieron aceite de palma y fue desplazada significativamente a la izquierda (p<0,01) en los que recibieron aceite de maíz. En conclusión los animales normocolesterolémicos, el suplemento de aceite de palma aumenta el colesterol a predominio de la fracción de HDL y sensibiliza la relajación dependiente del endotelio. El aceite de maíz aumenta la relajación arterial dependiente e independiente del endotelio adicionalmente atenúa la vasoconstricción mediana por el receptor adrenérgico &

Cardiovascular excitatory effect on rats of a fraction isolated from the eyestalk of shrimp: peneaus vanameii

El sistema nervioso de crustáceos es una fuente importante de sustancias con actividad biológica diversa, particularmente la que afecta la fisiología cardiocirculatoria de los invertebrados. Sin embargo, los efectos de estas sustancias sobre el sistema cardiovascular de mamíferos no están bien documentados. El objetivo de este estudio, fue evaluar los efectos de una sustancia cardioexcitatoria (SCE) aislada del tallo óptico del camarón Peneaus vanameii sobre la función cardiovascular de la rata. La administración de una fracción purificada de esta sustancia incrementó la presión arterial media en 37,33 ± 5,0 mm de Hg, la presión arterial diferencial en 35,00 ± 4,93 mm de Hg, así como la frecuencia cardiaca 80,00 ± 12,83 lat/min sobre los valores basales (p < 0,01). La evaluación del mecanismo por el cual este efecto hipertensor y taquicardizante se produjo indicó que el tratamiento con dihidroergotamina (20 µg/0,2 mL) redujo los efectos del SCE sobre la presión arterial media, pero no sobre la frecuencia cardiaca. El pretratamiento con propranolol (4 µg/0,2 mL) redujo la taquicardia pero no la respuesta hipertensiva. El pretratamiento con enalapril (5 µg/0,2 mL) no modificó los efectos inducidos por SCE sobre el corazón o los vasos sanguíneos, el pretratamiento con verapamil (1 µg/0,2 mL) redujo ambos cambios cardiovasculares en un 85 por ciento (p < 0,01). Estos resultados indican que el SCE aislado del tallo óptico del camarón produce hipertensión y taquicardia mediada a través de receptores adrenérgicos, en asociación con una activación de los canales de calcio

Efecto inotropico negativo directo de la cocaina en ventriculo de rata / Direct negative inotropic effect of cocaine in rat ventricle strip

Cocaine, when used as a recreative drug, can induce cardiovascular toxic effects such as acute reduction of left ventricle ejection fraction, which indicates a negative inotropic effect of the drug. The purpose of this study was to clarify the direct negative inotropic effect of cocaine in in vitro conditions. Rat right ventricle strips were incubated in Krebs solution gassed with 95 percent O2 and 5 percent CO2 at 37 degrees, and electrically driven with 2 ms square pulses, 17 mA, at 110 systoles/min. Separate experiments were conducted to study cocaine effect at 210 and 310 systoles/min. The contractile force was recorded through a strain-gauge isometric transducer. Cocaine increased contractile force at doses of 0.3-10.0 micrograms/ml, up to 53 percent over basal contraction. In the presence of 4 x 10(-8) Matenolol, low doses of cocaine did not increase contractile force and at doses between 3.0-10.0 micrograms/ml revealed a depressant activity on heart muscle contractions. Doxazosin (1.0 microM) and yohimbine (0.1 microM) did not modify the positive inotropic effect of cocaine, showing that alpha 1 and alpha 2 adrenergic receptors were not involved in this cocaine ventricle action. Increasing ventricle strip stimulation rate to 210 and 310 systoles/min for 30 seconds, the contractile force was risen by 55 percent and 95 percent, respectively. Cocaine at doses 1.0-3.0 micrograms/ml did not modify the physiological increase of contractile force seen upon ventricle rate increase. The mechanism involved in the contractile force increment after ventricle rate increase is a transient rise of cytosolic Ca2+, mainly derived from the sarcoplasmic reticulum and from extracellular fluid. Atenolol (4 x 10(-8) M) exposure of the right ventricle strip intensified the negative inotropic effect of cocaine (3.0-10 micrograms/ml) seen by ventricle stimulation at 210 and 310 systoles/min. The miocardial direct depressant effect of cocaine, in the presence of atenolol, was gradually reversed by extracelular Ca2+ increase at 3.2 and 5.0 mM, respectively. In conclusion, the mechanism of myocardial direct depressant effect of cocaine is related to the beating frequency of the ventricle, which may be sociated to interference with the Ca2+ release process from the myocite sarcoplasmic reticulum, and not to calcium entry blockade from extracellular fluid...

Efecto del carbacol inyectado en el ventriculo lateral cerebral sobre la actividad de acetilcolinesterasa de cinco áreas cerebrales de la rata / Effect of carbachol injected in the lateral ventricule on acetylcholinesterase activity of rat brain

El carbacol inyectado en el ventrículo lateral del cerebro (5 µg/5 µl) no produjo cambios en la actividad de la acetilcolinesterase (AChE) de la corteza cerebral a las dos horas después de la inyección. En el tallo cerebral se observó una ligera y transitoria disminución de la actividad de AChE (-12 por ciento), pero sólo en la fracción solubre de la enzima. En el hipocampo se observó una disminución moderada de la actividad de la fracción soluble de AChE a los 30 min post-inyección (-33.4 por ciento). Un cambio de similar magnitud se observó en el hipotálamo entre las 2-4 horas post-inyección. En el estriatum se observó una disminución de la fracción soluble de AChE (-45.3 por ciento) a los 30 min. post-inyección, que se recuperó a las 2 horas. La atropina, administrada por vía intraperitoneal (3-10 mg/kg) antagonizó los efectos del carbacol sobre la actividad de la enzima, así como también sus efectos catalépticos y tremorigénicos. Los resultados sugieren la presencia de receptores colinergicos de tipo muscarínico que al ser activados promueven la liberación de la enzima AChE soluble, de las neuronas activadas con carbacol

Desarrollo de un pletismografo de impedancia para evaluar la hiperemia reactiva en el antebrazo / Design of an impedance pletismograph for reactive hyperemia evaluation in the forearm

La pletismografía de impedancia se basa en medición del cambio de voltaje que ocurre por las variaciones de volumen que suceden en una sección de tejido. La corriente aplicada es del tipo alterna, débil y de alta frecuencia para evitar la estimulación de tejidoseléctricamente excitables como músculo y nervio. Los cambios de flujo sanguíneo son susceptibles de medición por este método y el mismo se ha aplicado en el diagnóstico de la oclusión venosa de los miembros. Se diseñó y construyó un medidor de impedancia para aplicarlo al antebrazo, el cual consta de un regulador de voltaje TPS76150 con registro simultaneo de la derivación DII del ECG. La señal de inyección generada fue de 50 KHz (puente de Wien) y registrada con dos amplificadores operacionales de transconductancia LM 3080 (1mA). Laseñal fue demodulada y reamplificada. Se usaron electrodos de banda de plata aplicados sobre la piel del antebrazo con gel de conducción eléctrica y sujetados con bandas de goma. El circuito y el software de adquisición fueron desarrollados en el centro de Bioingeniería de laUSB. Se hicieron registros en 15 sujetos sanos de 18-30 años de edad con protocolos de oclusión de la arteria braquial y registro de flujo sanguíneo en el antebrazo. Se hicieron oclusiones con un brazalete a presiones subdiastólica (oclusión venosa), supradiastólica ysuprasistólica; durante 60 y 90 segundos con liberación brusca de la oclusión. El gráfico se observó y registró en una computadora portátil (laptop). Durante la oclusión suprasistólica se halló un aumento inicial de impedancia progresivo hasta su estabilización y la aparición de unpico correspondiente a la hiperemia reactiva del antebrazo al momento de liberar la oclusión, el cual se ha relacionado con la liberación de sustancias vasodilatadores de origen endotelial. En conclusión, el aparato diseñado es de aplicación clínica sencilla, permite evaluar las variables hemodinámicas típicas de la hiperemia reactiva y es potencialmente utilizable en el diagnóstico de oclusiones venosas.

Decreased cardiovascular responses to cisterna magna NaCI injection in hypertensive rats

Albino rats were made hypertensive by 1 percent NaCl in the drinking water for 4-5 months, systolic (SBP) and distolic blood pressure (DBP) were 164.0 +/- 10.1 mm Hg and 118.7 +/- 4.6 mm Hg respectively, vs. control rats whose SBP and DBP were 119.0 +/- 4.4 mm Hg and 86.8 +/- 4.3 mm Hg respectively. Psychosocial stress (1 hour daily for 4-5 months) only raised SBP to 140.0 +/- 5.2 mm Hg; DBP remained unaltered. One percent NaCl intake combined with psychosocial stress, increased SBP and DBP but not significantly beyond the level observed with single 1 percent NaCl administration. Formerly described control and hypertensive rats were anesthetized with sodium pentobarbital (40 mg/kg) and stereotaxically injected into de cisterna magna (i.c.) with 20 microliters of 1.5 M NaCl solution. During i.c. injection, intraarterial SBP, DBP and heart rate (HR) were continuously recorded. After i.c., 1.5 M NaCl injection, mean arterial pressure (MAP) increased 21.0 +/- 4.0 mm Hg and HR 51.0 +/- 5.0 beats/min in control rats. Rats made hypertensive by 1 percent NaCl intake showed a significantly lower increase of MAP, 11.0 +/- 1.8 mm Hg; HR increased 37.0 +/- 4.3 beats/min. Rats submitted only to psychosocial stress displayed a response similar to the one described in control rats. Hypertensive rats submitted to both 1 percent NaCl intake and psychosocial stress had a more intense reduction of the hypertensive and tachycardic response, 8.0 +/- 2.2 mm Hg and 20.0 +/- 3.2 beats/min respectively. Control i.c. injection with the same volume of saline (0.15 M NaCl) did not change significantly SBP, DBP or HR in a separate group of rats. Left ventricle weight (0.754 +/- 0.0333 g) was augmented in the 1 percent NaCl treated group (0.795 +/- 0.038 g), and increased its protein content by 13.1 percent changes not statistically significant). The highest increase of the left ventricle weight (23.7 percent above control) with no change in its protein content was observed in rats submitted to 1 percent NaCl intake plus psychosocial stress. In conclusion, chronic high NaCl intake increased blood pressure; psychosocial stress acted as a weak stimulus for SBP and DBP increase, and central nervous system sodium chloride sensitivity for delivering a peripheral sympathetic discharge was found decreased in rats made hypertensive by a high salt intake

Increase of acetylcholinesterase activity of the cerebrospinal fluid of the rabbit after sciatic nerve stimulation, its blockade by atropine

El líquido cefalorraquideo (LCR) extraído de la cisterna magna del conejo anestesiado con pentobarbital posee actividad de acetilcolinesterasa (AChE). La estimulación eléctrica del nervio ciático aumentó la actividad de AChE del LCR y este efecto fue antagonizado fuertemente por la administración sistémica previa de sulfato de atropina (3 mg/kg) y no por la administración de metilnitrato de atropina (3 mg/kg). Durante los experimentos, la presión del LCR y la presión sanguínea sufrieron cambios despreciables; y la barrera hematoencefálica permaneció estable porque no se detectó azul de Evans en el tejido nervioso ni en el LCR. No se detectaron cambios en la acti-actividad de la LDH del LCR después de la estimulación del nervio ciático. En conclusión, el aumento de activdad de la AChE del LCR inducido por la estimulación nerviosa periférica parece estar mediado por un mecanismo colinérgico central

Mobilization of hypothalamus acetylcholinesterase from bound to soluble fraction by electrical stimulation of the rabbit sciatic nerve

La estimulación elétrica del nervio ciático del conejo produce un aumento significativo del porcentaje de actividad de acetilcolinesterasa (AChE) soluble del hipotálamo; aumenta en forma no significativa estadísticamente en el tálamo y no produce inigún cambio en el tallo cerebral. Este aumento de la actividad de AChE souble probablemente representa la movilización de la enzima desde el reticulo endoplásmico liso y rugoso hacia el citoplasma neuronal producto de la activación del sistema nervioso central evocado por la estimulación del nervio ciático