Effects of exercise training on circulating and skeletal muscle renin-angiotensin system in chronic heart failure rats.

BACKGROUND: Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. METHODS/MAIN RESULTS: Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. CONCLUSIONS: Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal muscle.

Repercussão funcional da disfunção endotelial venosa na hipertensão arterial sistêmica: correlação entre função endotelial e complacência venosas e débito cardíaco / Functional repercussion of venous endothelial dysfunction in systemic arterial hypertension: correlation between venous endothelial function and venous compliance and cardiac output

Enquanto há inúmeros trabalhos evidenciando a participação do território arterial na fisiopatologia da Hipertensão Arterial Sistêmica (HAS), pouco ainda se conhece da real participação do território venoso nessa doença. Estudos prévios demonstraram menor complacência venosa até mesmo em pacientes hipertensos limítrofe, e esta alteração não pode ser explicada como sendo apenas conseqüente a alteração do sistema simpático. Acrescidos a estas alterações, foi demonstrada disfunção endotelial no território venoso em pacientes com fatores de risco cardiovascular, incluindo HAS. Entretanto, ainda existem poucas informações sobre a correlação da disfunção endotelial venosa e/ou da capacitância e complacência venosas e seu impacto funcional na HAS. Neste protocolo foram avaliados 27 indivíduos do Grupo Controle (GC) (idade de 36,8±9,2 anos, 13 homens, IMC de 24,6±4,6 Kg/m2) e 31 pacientes do Grupo Hipertenso (GH) (idade de 38,2±10,5 anos, 15 homens e IMC de 26,1±3,1 Kg/m2). Curvas de pressão arterial (PA) foram obtidas de forma não invasiva com o Finometer®, durante 10 minutos de repouso na posição supina (basal) e durante 10minutos em manobra de modulação de volume (Tilt test). Por meio da análise das curvas, foram calculadas variáveis hemodinâmicas [PA sistólica e diastólica (PAS e PAD), freqüência cardíaca (FC), débito cardíaco (DC), índice cardíaco (CI), índice de volume sistólico (SVI) e índice de resistência vascular periférica (PRI)], além de ser realizada a análise espectral da FC (VFC) e da PAS (VPA). A capacitância e complacência venosas do antebraço foram aferidas por meio da pletismografia e a função endotelial venosa pela técnica da veia dorsal da mão (DHV), ambas avaliadas somente no momento basal. Resultados: O padrão hemodinâmico: o GH comparado com o GC apresentou maior PAS e PAD no momento basal (p<0,05). Em resposta ao Tilt test, houve: aumento de FC (p<0,05), diminuição da PAS (p<0,05), do DC (p<0,05), do CI (p<0,05) e do SVI (p<0,05) em ambos...

While there are numerous studies showing the involvement of the arteries in the pathophysiology of systemic arterial hypertension (AH), less is known about the role of the venous system in this disease. Previous studies have demonstrated lower venous compliance in established and borderline hypertensive patients, and this change can not be explained only by an increase in sympathetic activity. It is hypothesized that a lower venous compliance may have an impact on cardiac filling pressures and consequently on blood pressure levels. Furthermore, venous endothelial dysfunction, characterized by a decrease in venous dilation, was detected in patients with AH and with other cardiovascular risk factors. Therefore, we aimed to establish a correlation between venous endothelial dysfunction with venous compliance, and with venous compliance with different hemodynamic parameters. Casuistic and Methods: a total of 31 patients with stage 1 and 2 of AH (HG) (age of 38.2 ± 10.5 years, 15 men and BMI of 26.1 ± 3.1 kg/m2) and 27 normotensive subjects the control group (CG) (age 36.8 ± 9.2 years, 13 men, BMI 24.6 ± 4.6 kg/m2) were evaluated. Curves of blood pressure (BP) were obtained non-invasively with Finometer ® device, and were recorded for 10-minute in both supine (baseline) position and during tilt test maneuver. By analyzing the curves, hemodynamic variables [systolic and diastolic BP (SBP and DBP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume index (SVI) and index vascular resistance (IVS)], and spectral analysis of HR (HRV) and SBP (BPV) were performed. The venous capacitance and compliance of the forearm were measured by plethysmography and venous endothelial function by the technique of dorsal hand vein (DHV), both assessed only at baseline. Results: At baseline, the HG showed a different hemodynamic pattern compared to the CG, with higher SBP and DBP. In response to the tilt test, both groups presented a similar response...