Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice

Abstract Purpose: To determine whether the absence of transglutaminase 2 enzyme (TG2) in TG2 knockout mice (TG2-/-) protect them against early age-related functional and histological arterial changes. Methods: Pulse wave velocity (PWV) was measured using non-invasive Doppler and mean arterial pressure (MAP) was measured in awake mice using tail-cuff system. Thoracic aortas were excised for evaluation of endothelial dependent vasodilation (EDV) by wire myography, as well as histological analyses. Results: PWV and MAP were similar in TG2-/-mice to age-matched wild type (WT) control mice. Old WT mice exhibited a markedly attenuated EDV as compared to young WT animals. The TG2-/-young and old mice had enhanced EDV responses (p<0.01) as compared to WT mice. There was a significant increase in TG2 crosslinks by IHC in WT old group compared to Young, with no stain in the TG2-/-animals. Optical microscopy examination of Old WT mice aorta showed thinning and fragmentation of elastic laminae. Young WT mice, old and young TG2-/-mice presented regularly arranged and parallel elastic laminae of the tunica media. Conclusion: The genetic suppression of TG2 delays the age-induced endothelial dysfunction and histological modifications.

Vasodilation and Reduction of Systolic Blood Pressure after One Session of High-Intensity Interval Training in Patients With Heart Failure with Preserved Ejection Fraction / Vasodilatação e Redução da Pressão Arterial Sistólica após uma Sessão de Treinamento Intervalado de Alta Intensidade em Pacientes com Insuficiência Cardíaca com Fração de Ejeção Preservada

Abstract Background: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial syndrome characterized by a limited exercising capacity. High-intensity interval training (HIIT) is an emerging strategy for exercise rehabilitation in different settings. In patients with HFpEF, HIIT subacute effects on endothelial function and blood pressure are still unknown. Objective: To evaluate the subacute effect of one HIIT session on endothelial function and blood pressure in patients with HFpEF. Methods: Sixteen patients with HFpEF underwent a 36-minute session of HIIT on a treadmill, alternating four minutes of high-intensity intervals with three minutes of active recovery. Brachial artery diameter, flow-mediated dilation, and blood pressure were assessed immediately before and 30 minutes after the HIIT session. In all analyses, p <0.05 was considered statistically significant. Results: There was an increase in brachial artery diameter (pre-exercise: 3.96 ± 0.57 mm; post-exercise: 4.33 ± 0.69 mm; p < 0.01) and a decrease in systolic blood pressure (pre-exercise: 138 ± 21 mmHg; post-exercise: 125 ± 20 mmHg; p < 0.01). Flow-mediated dilation (pre-exercise: 5.91 ± 5.20%; post-exercise: 3.55 ± 6.59%; p = 0.162) and diastolic blood pressure (pre-exercise: 81 ± 11 mmHg; post-exercise: 77 ± 8 mmHg; p = 1.000) did not change significantly. There were no adverse events throughout the experiment. Conclusions: One single HIIT session promoted an increase in brachial artery diameter and reduction in systolic blood pressure, but it did not change flow-mediated dilation and diastolic blood pressure.

Resumo Fundamento: Insuficiência cardíaca com fração de ejeção preservada (ICFEP) é uma síndrome multifatorial caracterizada por limitação ao exercício. O treinamento intervalado de alta intensidade (HIIT) é uma estratégia emergente para a reabilitação do exercício em diferentes contextos. Em pacientes com ICFEP, os efeitos subagudos do HIIT sobre a função endotelial e a pressão arterial ainda são desconhecidos. Objetivo: Avaliar o efeito subagudo de uma única sessão do HIIT sobre a função endotelial e a pressão arterial em pacientes com ICFEP. Métodos: Dezesseis pacientes com ICFEP foram submetidos a uma sessão de 36 minutos de HIIT em esteira rolante, alternando quatro minutos de intervalos de alta intensidade com três minutos de recuperação ativa. O diâmetro da artéria braquial, a dilatação mediada pelo fluxo e a pressão arterial foram avaliados imediatamente antes e 30 minutos após a sessão de HIIT. Em todas as análises, p <0,05 foi considerado estatisticamente significativo. Resultados: Houve aumento do diâmetro da artéria braquial (pré-exercício: 3,96 ± 0,57 mm; pós-exercício: 4,33 ± 0,69 mm; p < 0,01), e diminuição da pressão arterial sistólica (pré-exercício: 138 ± 21 mmHg; pós-exercício: 125 ± 20 mmHg; p < 0,01). A dilatação mediada por fluxo (pré-exercício: 5,91 ± 5,20%; pós-exercício: 3,55 ± 6,59%; p = 0,162) e pressão arterial diastólica (pré-exercício: 81 ± 11 mmHg; pós-exercício: 77 ± 8 mmHg; p = 1,000) não se alteraram significativamente. Não houve eventos adversos durante o experimento. Conclusões: Uma única sessão do HIIT promoveu aumento do diâmetro da artéria braquial e redução da pressão arterial sistólica, mas não alterou a dilatação mediada pelo fluxo e a pressão arterial diastólica.

The role of potassium channels in the endothelial dysfunction induced by periodontitis

Abstract Objective: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. Material and methods: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. Results: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. Conclusions: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.

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.

Impaired flow-mediated dilation response and carotid intima-media thickness in patients with type 1 diabetes mellitus with a mean disease duration of 4 1 years

ABSTRACT Objective This study aimed at assessing the endothelial function in patients with Type 1 diabetes (T1DM) using flow-mediated dilation (FMD) response and carotid artery intima-media thickness (CIMT). Materials and methods This study enrolled 32 T1DM patients (mean disease duration 4.1 years) and 28 age-matched controls (CTL Group). Endothelial function and CIMT were assessed with high-resolution ultrasound using standardized offline measurements. Results FMD was significantly lower in patients in the T1DM Group (8.9 ± 3.2%) compared with those in the CTL Group (13.3 ± 4.3%; P-value < 0.0001). Similarly, CIMT differed significantly between T1DM patients (0.525 ± 0.03 mm) and controls (0.508 ± 0.03 mm; P-value = 0.041). Even though, the values are within the normal range for age. Conclusions Patients with T1DM have impaired endothelial function characterized by reduced FMD when compared to controls. However, vascular remodeling as seen by increases in CIMT was not found in this study.

Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats

OBJECTIVE: We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. METHODS: Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each) and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively). The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal’s body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M) with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M) in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. RESULTS: Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%). Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. CONCLUSIONS: In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving endothelial function.

Role of NO in arterial vascular function of intertidal fish (Girella laevifrons) and marine fish (Isacia conceptionis) / Papel do NO na função vascular arterial de peixes entremarés (Girella laevifrons) e peixes marinhos (Isacia conceptionis)

Abstract Previous studies performed in intertidal fish (Girella laevifrons),as well as marine fish (Isacia conceptionis), showed that acetylcholine (ACh) produced contractions mediated by cyclooxygenases that were dependent on the area and potency of contraction in several arterial vessels. Given that the role of nitric oxide is poorly understood in fish, the objective of our study was to evaluate the role of nitric oxide in branchial afferent (ABA), branchial efferent (ABE), dorsal (DA) and mesenteric (MA) arterial vessels from both Girella laevifrons and Isacia conceptionis. We studied afferent and efferent branchial, dorsal and mesenteric arteries that were dissected from 6 juvenile specimens. Isometric tension studies were done using dose response curves (DRC) for Ach (10–13 to 10–3 M) and blockade with L-NAME (10–5 M), and DRC for sodium nitroprusside (SNP, a donor of NO). L-NAME produced an attenuation of the contractile response in the dorsal, afferent and efferent branchial arteries and a potentiation of the contraction in the MA. SNP caused 70% dilation in the mesenteric artery and 40% in the dorsal artery. Our results suggest that Ach promotes precarious dilatation in MA mediated by NO; data that is supported by the use of sodium nitroprusside. In contrast, in the vessels DA, ABA and EBA our results support that the pathway Ach-NO-relaxation is absent in both species.

Resumo Estudos anteriores, realizados no peixe intertidal (Girellalaevifrons) no peixe marinho (Isacia conceptionis), mostram que a acetilcolina (Ach) provoca contrações mediadas por ciclooxigenases que eram dependentes da área e potencia da contração em vários vasos arteriais. Tendo em conta que o papel do óxido nítrico é mal compreendido em peixes, o objetivo do nosso estudo foi avaliar o papel do óxido nítrico em vasos arteriais de ambos os peixes Girella laevifrons e Isacia conceptionis. Nós estudamos os vasos aferente, branquial (ABA), eferente branquial (ABE), dorsal (DA) e mesentérica (MA), que foram dissecadas de seis espécimes juvenis. Estudos de tensão isométrica foram realizados utilizando as curvas de dose-resposta (DRC) para Ach (10–13 a 10–3M) e bloqueio com L-NAME (10–5 M), e na DRC para o nitroprussiato de sódio (SNP, doador do NO). L- NAME produziu uma atenuação da resposta contrátil nas artérias dorsais, aferentes e eferentes branquial e uma potenciação da contração no MA. SNP causaram 70% da dilatação da artéria mesentérica e 40% na artéria dorsal. Nossos resultados sugerem que Ach promove dilatação precária em MA mediada por NO; dados que é suportada pela utlilização de nitroprussiato de sódio. Em contraste, nos vasos de DA, ABA e EBA nossos resultados suportam que a via de Ach-NO-relaxamento está ausente em ambas as espécies.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.

Association between periodontal disease and endothelial dysfunction in smoking patients / Asociación entre enfermedad periodontal y disfunción endotelial en pacientes fumadores

Over the past two decades, there has been increasing interest inthe impact of oral health on cardiovascular disease, particularlyregarding the effects of chronic infections such as periodontitison the endothelium. The aim of this study was to evaluate inhealthy smokers whether there are any significant differences inthe frequency of endothelial dysfunction between subjects with chronic moderate to severe periodontal disease andperiodontally healthy subjects. An observational cross-sectionalstudy was conducted. The target population was adults olderthan 40 years of age. Blood tests were performed to determinevalues of CBC, glycaemia, total cholesterol, HDL-C, and LDL-C. Periodontal examinations and probing were conducted witha Florida Probe®, and standardized procedures were used tomeasure flow-mediated dilation. Out of 150 subjects [69 male(46%) and 81 female (54%)], 75 (50%) had chronicperiodontitis. The mean value for baseline flow-mediateddilation was 4.04% and the mean value for final flow-mediateddilation was 4.66%, with a 0.62% mean difference showing astatistically significant increase (p<0.001).This study found nosignificant difference in the flow-mediated dilation valuesbetween periodontally healthy subjects and those withperiodontitis, in contrast to the literature, which suggests anegative impact of periodontal disease on endothelial function.

Durante las últimas dos décadas ha venido incrementándose el interés acerca del impacto de la salud oral, sobre las enfermedades cardiovasculares. El objetivo del estudiofue evaluar si en pacientes sistémicamente sanos y con tabaquismo, se encontraban diferencias significativas en la frecuencia de disfunción endotelial entre personas con enfermedad periodontal crónica de moderada a severa y personas con salud periodontal. El diseño empleado fue unestudio observacional de corte transversal. La población blanco, pacientes adultos mayores de 40 años de edad. Se tomaron muestras de sangre para obtener los valores de cuadro hemático, glucemia, colesterol total, cHDL y cLDL. Se realizó el examen periodontal diligenciando el anexo de periodoncia de la Facultad de Odontología y de acuerdo con el instructivo. El sondaje se realizó en todos los dientes presentes en bocautilizando la sonda electrónica periodontal (Florida Probe®). La técnica y procedimientos para la vasodilatación mediada por flujo utilizados fueron los estandarizados internacionalmente. De los 150 participantes, 69 eran hombres (46 por ciento) y 81 mujeres (54 por ciento) con promedio de edad de 50.2 años. De estos, 75 pacientes (50 por ciento) correspondían al grupo deperiodontitis crónica. Al evaluar la vasodilatación mediada por flujo elpromedio inicial encontrado fue de 4.04 por ciento y el final fue de4.66 por ciento, con un 0.62 por ciento de aumento en promedio (p<0.001). Sepuede concluir que a pesar de la evidencia en la literatura que sugiere que la enfermedad periodontal impacta negativamente la función endotelial, medida por vasodilatación mediadapor flujo, el presente estudio no encontró una diferencia significativa.

Função endotelial e tratamento periodontal não cirúrgico de pacientes diabéticos com periodontite / Endothelial function and non-surgical periodontal treatment in diabetic patients with periodontitis

O objetivo desse estudo foi investigar alterações na função endotelial, além de realizar meta-análises sobre o uso de antibióticos adjuvantes ao tratamento periodontal não cirúrgico em relação aos possíveis benefícios em termos de parâmetros clínicos periodontais e controle glicêmico nos pacientes diabéticos com periodontite. Quarenta e oito pacientes foram avaliados quanto aos parâmetros periodontais e função endotelial. Desses 48, 11 não tinham doença periodontal e não eram diabéticos (grupo A), 17 tinham periodontite crônica e não eram diabéticos (grupo B), e 20 tinham periodontite crônica e diabetes mellitus tipo 2 (grupo C). Dois revisores independentes examinaram ensaios clínicos controlados em 6 bases de dados eletrônicas, registros de ensaios clínicos, resumos de reuniões e 4 principais revistas odontológicas. A vasodilatação dependente do endotélio (fluxo de hiperemia) foi significantemente menor no grupo C quando comparado com os grupos A e B, assim como foi significantemente menor no grupo B quando comparado com o grupo A (p<0,05). As meta-análises mostraram um efeito significativo favorecendo tratamento periodontal associado a antibióticos para reduções na média de profundiade de sondagem (-0,22 mm [-0,34, -0,11]) e na média de porcentagem de sangramento a sondagem (4% [-7, -1]). Não houve efeito significativo no ganho de nível de inserção clínica e redução do índice de placa. Além disso, a associação de antibióticos e tratamento periodontal não reduziu os valores de hemoglobina glicada média (-0,11% [-0,35, 0,13]), e um intervalo de previsão estimado variando de -0,45 a 0,23. Também não houve efeito significativo favorecendo o uso adjuvante de doxiciclina sub-antimicrobiana na redução média da hemoglobina glicada (-0,19% [-1,07, 0,68]). Sendo assim, pode-se concluir que a periodontite crônica está associada a diminuição da vasodilatação dependente do endotélio do indivíduo, assim como diminui ainda mais quando associada ao diabetes mellitus. O antibiótico sistêmico adjuvante ao tratamento periodontal proporciona benefícios estatisticamente significantes em termos de reduções de média de profundidade de bolsa a sondagem e o percentual de sangramento a sondagem, porém não proporciona um benefício significativo em termos de melhoria de nível de inserção clínico, índice de placa e hemoglobina glicada.

The aim of this study was to investigate alterations in endothelial function, besides performing meta-analyzes on the use of adjuvant antibiotics to non-surgical periodontal treatment in relation to the possible benefits in terms of periodontal clinical parameters and glycemic control in diabetic patients with periodontitis. Forty-eight patients were evaluated for periodontal parameters and endothelial function. Of these, 11 h ad no periodontal disease and were not diabetic (group A), 17 had chronic periodontitis and were not diabetic (group B), and 20 had chronic periodontitis and type 2 diabetes mellitus (group C). Two independent reviewers examined controlled clinical trials in 6 electronic databases, clinical trial records, meeting summaries, and 4 major dental journals. Endothelium-dependent vasodilation (hyperemia flow) was significantly lower in group C when compared to groups A and B, as well as significantly lower in group B when compared to group A (p <0.05). The meta-analyzes showed a significant effect favoring antibiotic-associated periodontal treatment for reductions in the mean probing pocket depth (-0,22 mm [-0,34; -0,11]) and the mean percentage of bleeding probing ( 4% [-7, -1]). There was no significant effect on gain of clinical attachment level and reduction of plaque index. In addition, the association of antibiotics and periodontal treatment did not reduce mean glycated hemoglobin values (-0,11% [-0,35, 0,13]), and an estimated prediction interval ranging from -0,45 to 0,23. There was also no significant effect favoring the adjuvant use of sub-antimicrobial doxycycline in the mean reduction of glycated hemoglobin (-0,19% [-1,07, 0,68]). Thus, it may be concluded that chronic periodontitis is associated with decreased vasodilatation dependent on the endothelium of the individual, as well as decreases even more when associated with diabetes mellitus. The systemic antibiotic adjuvant to periodontal treatment provides statistically significant benefits in terms of reductions of mean probing pocket depth and % of bleeding on probing, but does not provide a significant benefit in terms of improvement of clinical attachment level, plaque index and glycated hemoglobin.

Role of adenylyl cyclase in reduced ß-adrenoceptor-mediated vasorelaxation during maturation

Beta-adrenergic receptor (βAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of βAR subtypes (β1AR, β2AR, and β3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of βAR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of βAR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744-dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The β1AR antagonist CGP20712A (10-7 M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The β2AR antagonist ICI-118,551 (10-7 M) inhibited isoproterenol-dependent aortic relaxation in both groups. The β3AR antagonist SR59230A (10-7 M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All βAR subtypes were expressed in both groups, although β3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of β3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group.

Vasodilatación mediada por flujo en niños con sobrepeso / Flow mediated vasodilation in overweight children

Introducción: El conocimiento actual sugiere que la enfermedad cardiovascular se origina y progresa desde la infancia y la adolescencia. La disfunción endotelial es un evento temprano y crucial en la aterosclerosis. Pacientes y Método: Estudio prospectivo que comparó la vasodilatación mediada por flujo (VMF) en niños con sobrepeso y niños de peso normal. Para medir la VMF se utilizó transductor adecuado de ultrasonido y el método estándar. Resultados: Ochenta y dos niños fueron incluidos; 49 eran casos (sobrepeso) y 33 controles. Los valores de VMF oscilaron entre -6 y 56% (promedio 11,1%) en niños con sobrepeso y de 0 a 29,6% (promedio 16,6%) en niños control (p < 0,05). Se presentó vasoconstricción paradójica en el 34,7% de los niños con sobrepeso y en ninguno de los controles (p < 0,05). Se encontró una asociación significativa entre vasoconstricción paradójica con obesidad central e hipertensión. Conclusión: Los resultados de este estudio muestran que la VMF es menor en niños con sobrepeso en comparación con los niños eutróficos, por lo que es más probable que exista disfunción endotelial en ellos.

Introduction: Present knowledge suggests that cardiovascular disease originates and progresses from childhood and adolescence. Endothelial dysfunction is an early and crucial event in atherosclerosis. Patients and Method: Prospective study that compares Flow Mediated Vasodilation (FMV) in children with overweight (OWC) and normal weight children. An ultrasound transducer a standard method were used to measure FMD. Results: The study included 82 children, of whom 49 were cases (OWC) and 33 controls. FMV values ranged from -6 to 56% (x = 11.1%) in OW, and from 0 to 29.6% (x = 16.6%) in control children (P<.005). Paradoxical vasoconstriction was found in 34.7% in OWC as compared to nil in controls (P<.005). A significant association was found between vasoconstriction and central obesity and hypertension. Conclusion: The results of this study show that FMV is lower in obese compared to normal children; thus they are more likely to have endothelial dysfunction.

Intensity of swimming exercise influences aortic reactivity in rats

Exercise is known to cause a vasodilatory response; however, the correlation between the vasorelaxant response and different training intensities has not been investigated. Therefore, this study evaluated the vascular reactivity and lipid peroxidation after different intensities of swimming exercise in rats. Male Wistar rats (aged 8 weeks; 250-300 g) underwent forced swimming for 1 h whilst tied to loads of 3, 4, 5, 6, and 8% of their body weight, respectively (groups G3, G4, G5, G6 and G8, respectively; n=5 each). Immediately after the test, the aorta was removed and suspended in an organ bath. Cumulative relaxation in response to acetylcholine (10−12-10−4 M) and contraction in response to phenylephrine (10−12-10−5 M) were measured. Oxidative stress was estimated by determining malondialdehyde concentration. The percentages of aorta relaxation were significantly higher in G3 (7.9±0.20), G4 (7.8±0.29), and G5 (7.9±0.21), compared to the control group (7.2±0.04), while relaxation in the G6 (7.4±0.25) and G8 (7.0±0.06) groups was similar to the control group. In contrast, the percentage of contraction was significantly higher in G6 (8.8 ±0.1) and G8 (9.7±0.29) compared to the control (7.1±0.1), G3 (7.3±0.2), G4 (7.2±0.1) and G5 (7.2±0.2%) groups. Lipid peroxidation levels in the aorta were similar to control levels in G3, G4 and G5, but higher in G6 and G8, and significantly higher in G8 (one-way ANOVA). These results indicate a reduction in vasorelaxing activity and an increase in contractile activity in rat aortas after high-intensity exercise, followed by an increase in lipid peroxidation.

Andreas Vesalius as a renaissance innovative neuroanatomist: his 5th centenary of birth / Andreas Vesalius como neuroanatomista inovador renascentista: seu 5° centenário de nascimento

Andreas Vesalius (1514-1564) is considered the Father of Modern Anatomy, and an authentic representative of the Renaissance. His studies, founded on dissection of human bodies, differed from Galeno, who based his work on dissection of animals, constituted a notable scientific advance. Putting together science and art, Vesalius associated himself to artists of the Renaissance, and valued the images of the human body in his superb work De Humani Corporis Fabrica.This paper aims to honor this extraordinary European Renaissance physician and anatomist, who used aesthetic appeal to bind text and illustration, science and art. His achievements are highlighted, with an especial attention on neuroanatomy. Aspects about his personal life and career are also focused.

Andreas Vesalius (1514-1564) é considerado o Pai da Anatomia Moderna e um autêntico representante da Renascença. Seus estudos, baseados na dissecação de corpos humanos, diferiam dos de Galeno, que baseava seu trabalho em dissecação de animais, constituiu-se em um notável avanço científico. Reunindo ciência e arte, Vesalius associou-se a artistas da Renascença e valorizou as imagens do corpo humano em seu soberbo trabalho De Humani Corporis Fabrica. Este artigo visa honrar esse extraordinário médico e anatomista da Renascença europeia, que fez uso do apelo estético para coligar texto e ilustração, ciência e arte. Suas realizações são realçadas, com atenção especial na neuroanatomia. Também são colocados em foco aspectos da sua vida pessoal e de sua carreira.

Prejuízo da vasodilatação muscular durante estresse mental em mulheres com hipotireoidismo subclínico / Impairment of muscle vasodilation during mental stress in women with subclinical hypothyroidism

Objetivo Testar a hipótese de que mulheres com hipotireoidismo subclínico (HSC) possuem condutância vascular do antebraço (CVA) prejudicados durante estresse mental. Sujeitos e métodos Foram avaliadas 20 mulheres com HSC e 21 eutireoidianas (Grupo Controle), pareadas por idade (p = 0,699) e índice de massa corporal (p = 0,462). O fluxo sanguíneo muscular (FSM), avaliado pela pletismografia de oclusão venosa, e a pressão arterial, medida pelo Dixtal2023, foram registrados simultaneamente durante 3 minutos de basal, seguidos de 3 minutos de estresse mental. A CVA foi calculada pela divisão do FSM pela pressão arterial média. Foi adotada significância de p < 0,05. Resultados O grupo HSC apresentou maior concentração do hormônio tireoestimulante (7,57 ± 3,17 vs. 2,10 ± 0,88 mU/L, p < 0,001). No basal, os grupos HSC e Controle foram semelhantes respectivamente para FSM (2,50 ± 0,79 vs. 2,55 ± 0,71 mL/min/100 mL, p = 0,905) e CVA (2,80 ± 0,90 vs. 2,92 ± 0,88 unidades, p = 0,952). Durante todo o estresse mental, os grupos HSC e Controle aumentaram significativamente o FSM (efeito tempo, p < 0,001) e CVA (efeito tempo, p < 0,001) em relação ao basal. Porém, essas variáveis foram significativamente menores no grupo HSC durante o primeiro (FSM: 3,66 ± 0,96 vs. 4,66 ± 1,61 mL/ min/100 mL, p = 0,018; CVA: 3,95 ± 1,08 vs. 5,19 ± 1,96 unidades, p = 0,010) e segundo (FSM: 3,55 ± 1,01 vs. 4,62 ± 2,27 mL/min/100 mL, p = 0,018; CVA: 3,75 ± 1,07 vs. 4,92 ± 2,37 unidades, p = 0,020) minutos do teste de estresse mental. Conclusão Mulheres com HSC possuem comportamento vasodilatador prejudicado durante o estresse mental. .

Objective To test the hypothesis that women with subclinical hypothyroidism (SH) have forearm vascular conductance (FVC) impaired during mental stress. Subjects and methods We evaluated 20 women with SH and 21 euthyroid (Control group), matched for age (p = 0.699) and body mass index (p = 0.462). Muscle blood flow (MBF) was assessed by venous occlusion plethysmography and blood pressure by Dixtal2023. Both variables were recorded simultaneously for 3 minutes of baseline followed by 3 minutes of mental stress. The FVC was calculated by dividing MBF by mean arterial pressure. Significant differences were assumed at p < 0.05. Results The SH group had higher concentrations of thyroid stimulating hormone (7.57 ± 3.17 vs. 2.10 ± 0,88 mU/L, p < 0.001). At baseline, the SH and control groups were similar for MBF (2.50 ± 0.79 vs. 2.55 ± 0,71 mL/ min/100 mL, p = 0.905, respectively) and FVC (2.80 ± 0.90 vs. 2.92 ± 0.88 units, p = 0.952, respectively). Throughout the mental stress test the SH and Control groups increased the MBF (time effect, p < 0.001) and FVC (time effect, p < 0.001) compared to baseline protocol. However, these variables were lower in SH group during the first (MBF: 3.66 ± 0.96 vs. 4.66 ± 1,61 mL/min/100 mL, p = 0.018, FVC: 3.95 ± 1.08 vs. 5.19 ± 1,96 units, p = 0.010) and second (MBF: 3.55 ± 1.01 vs. 4.62 ± 2,27 mL/min/100 ml, p = 0.018; FVC: 3.75 ± 1.07 vs. 4.92 ± 2,37 units, p = 0.020) minutes of mental stress test. Conclusion Women with SH have reduced muscle vasodilatatory response during mental stress. .

Daily assessment of arterial distensibility in a pediatric population before and after smoking cessation

OBJECTIVES: Cigarette smoking is an important modifiable cardiovascular risk factor associated with increased stiffness of the large arteries in adulthood. This study aimed to 1) evaluate arterial distensibility and echocardiographic measures in adolescent smokers before and after participation in a successful smoking cessation program and to 2) compare the findings obtained with data from a control population of healthy non-smokers. METHODS: A total of 31 young smoking subjects (58.1% male; range: 11-18 years old; mean: 16.5±1.4 years old; mean tobacco consumption: 2.6±0.6 years) were examined before commencing and after taking part for at least 1 year in a smoking cessation program (mean: 1.4±0.3 years). Arterial stiffness was measured using the previously validated QKd100-60 method. Twenty-four-hour ambulatory blood pressure monitoring and transthoracic echocardiography were also performed. RESULTS: (Smokers before abuse cessation vs. smokers after abuse cessation) systolic blood pressure: p<0.004; diastolic blood pressure: p<0.02; mean blood pressure: p<0.01; QKd100-60 value: 183±5 vs. 196±3 msec, p<0.009; p = ns for all echocardiographic parameters. (Smokers after abuse cessation vs. controls) systolic blood pressure: p<0.01; diastolic blood pressure: p<0.03; mean blood pressure: p<0.02; QKd100-60 value: 196±3 vs. 203±2 msec, p<0.04; p<0.02, p<0.01, and p<0.05 for the interventricular septum, posterior wall, and left ventricular mass, respectively. CONCLUSIONS: Despite successful participation in a smoking cessation program, arterial distensibility improved but did not normalize. This finding underlines the presence of the harmful effect of arterial rigidity in these individuals, despite their having quit smoking and their young ages, thus resulting in the subsequent need for a lengthy follow-up period. .

Interferential electrical stimulation improves peripheral vasodilatation in healthy individuals

BACKGROUND: Interferential electrical stimulation (IES), which may be linked to greater penetration of deep tissue, may restore blood flow by sympathetic nervous modulation; however, studies have found no association between the frequency and duration of the application and blood flow. We hypothesized that 30 min of IES applied to the ganglion stellate region might improve blood flow redistribution. OBJECTIVES: The purpose of this study was to determine the effect of IES on metaboreflex activation in healthy individuals. METHOD: Interferential electrical stimulation or a placebo stimulus (same protocol without electrical output) was applied to the stellate ganglion region in eleven healthy subjects (age 25±1.3 years) prior to exercise. Mean blood pressure (MBP), heart rate (HR), calf blood flow (CBF) and calf vascular resistance (CVR) were measured throughout exercise protocols (submaximal static handgrip exercise) and with recovery periods with or without postexercise circulatory occlusion (PECO+ and PECO -, respectively). Muscle metaboreflex control of calf vascular resistance was estimated by subtracting the area under the curve when circulation was occluded from the area under the curve from the AUC without circulatory occlusion. RESULTS: At peak exercise, increases in mean blood pressure were attenuated by IES (p<0.05), and the effect persisted under both the PECO+ and PECO- treatments. IES promoted higher CBF and lower CVR during exercise and recovery. Likewise, IES induced a reduction in the estimated muscle metaboreflex control (placebo, 21±5 units vs. IES, 6±3, p<0.01). CONCLUSION: Acute application of IES prior to exercise attenuates the increase in blood pressure and vasoconstriction during exercise and metaboreflex activation in healthy subjects. .

Endothelial dysfunction in primary Sjögren syndrome / Disfunción endotelial en el síndrome de Sjögren primario

OBJECTIVE: In this study, we aimed to investigate endothelial functions in primary Sjögren syndrome. METHODS: Thirty-five patients with primary Sjögren syndrome and 20 age and sexmatched healthy volunteers were recruited to the present study. Flow mediated dilatation of brachial artery and carotid intimamedia thickness were measured in the study population. RESULTS: Carotid intimamedia thickness values were similar between groups (0.50 ± 0.10, 0.53 ± 0.08, p > 0.05). Flow mediated dilatation of the brachial artery was disrupted in the primary Sjögren syndrome group (7% vs 12%, p = 0.002). CONCLUSION: There is endothelial dysfunction in patients with primary Sjögren syndrome, although they had comparable carotid intimamedia thickness with the healthy control group.

OBJETIVO: Este estudio se encaminó a investigar las funciones endoteliales en el síndrome de Sjögren primario. MÉTODOS: Para el presente estudio, se reclutaron treinta y cinco pacientes con síndrome de Sjögren primario y 20 voluntarios sanos apareados por edad y sexo. La dilatación mediada por flujo observada en la arteria braquial, y el espesor íntimamedia carotídeo fueron medidos en la población bajo estudio. RESULTADOS: Los valores del espesor íntimamedia carotídeo fueron similares entre los grupos (0.50 ± 0.10, 0.53 ± 0.08, p > 0.05). La dilatación mediada por flujo de la arteria braquial, estaba alterada en el grupo de síndrome del Sjögren primario (7% frente a 12%, p = 0.002). CONCLUSIÓN: Hay una disfunción endotelial en los pacientes con el síndrome de Sjögren primario, aunque estos tenían un espesor íntimamedia carotídeo comparable con el grupo de control saludable.