Exercise training reduces renin-angiotensin system (RAS) activation, decreases plasma and tissue oxidative stress and inflammation in hypertension. However, the temporal nature of these phenomena in response to exercise is unknown. We sought to determine in spontaneously hypertensive rats (SHR) and age-matched WKY controls the weekly effects of training on blood pressure (BP), plasma and left ventricle (LV) Ang II and Ang-(1–7) content (HPLC), LV oxidative stress (DHE staining), gene and protein expression (qPCR and WB) of pro-inflammatory cytokines, antioxidant enzymes and their consequence on hypertension-induced cardiac remodeling. SHR and WKY were submitted to aerobic training (T) or maintained sedentary (S) for 8 weeks; measurements were made at weeks 0, 1, 2, 4 and 8. Hypertension-induced cardiac hypertrophy was accompanied by acute plasma Ang II increase with amplified responses during the late phase of LV hypertrophy. Similar pattern was observed for oxidative stress markers, TNF alpha and interleukin-1β, associated with cardiomyocytes’ diameter enlargement and collagen deposition. SHR-T exhibited prompt and marked decrease in LV Ang II content (T1 vs T4 in WKY-T), normalized oxidative stress (T2), augmented antioxidant defense (T4) and reduced both collagen deposition and inflammatory profile (T8), without changing cardiomyocytes’ diameter and LV hypertrophy. These changes were accompanied by decreased plasma Ang II content (T2-T4) and reduced BP (T8). SHR-T and WKY-T showed parallel increases in LV and plasma Ang-(1–7) content. Our data indicate that early training-induced downregulation of LV ACE-AngII-AT1 receptor axis is a crucial mechanism to reduce oxidative/pro-inflammatory profile and improve antioxidant defense in SHR-T, showing in addition this effect precedes plasma RAS deactivation.

Although the use of exercise as a therapeutic tool has increased considerably, there is scarce information on the mechanisms conditioning the beneficial effects of training. Previous observations indicate the ability of training to reduce either the activity of the renin-angiotensin system (RAS), oxidative stress and inflammation. 10-12 By evaluating the effects of low-intensity aerobic training on the expression of brain RAS in cardiovascular-controlling areas of spontaneously hypertensive rats (SHR), we observed a prompt and robust training-induced reduction of either angiotensinogen (Aogen) ccumulating experimental evidence has shown that exercise training is an efficient and safe tool to counteract deleterious effects induced by hypertension, coronary artery disease and other cardiovascular diseases. 1-3 Exercise training promotes several cardiovascular adjustments in hypertensive and normotensive individuals, such as remodeling of the heart with a simultaneous stroke volume increase and heart rate (HR) decrease, 1,2,4,5 outward eutrophic remodeling of arteries and arterioles, capillary angiogenesis, and venule neoformation in the exercised muscles. 6-8 Aerobic training also restores impaired endothelial function in hypertensive animals and facilitates artery/arteriole vasodilatation. 2,9 These adaptive mechanisms, by reducing vascular resistance and improving both blood flow and tissue conductance, ameliorate Background: Hyperactivity of the renin-angiotensin system (RAS) and functional deficits in hypertension are reduced after exercise training. We evaluate in arteries, kidney and plasma of hypertensive rats the sequential effects of training on vascular angiotensinogen, Ang II and Ang (1-7) content.

GABA ergic inhibitory input within the paraventricular hypothalamic nucleus ( PVN ) plays a key role in restraining sympathetic outflow. Although experimental evidence has shown depressed GABA A receptor function plus sympathoexcitation in hypertension and augmented GABA levels with reduced sympathetic activity after exercise training (T), the mechanisms underlying T‐induced effects remain unclear. Here we investigated in T and sedentary (S) S HR and WKY : (1) time‐course changes of hemodynamic parameters and PVN glutamic acid decarboxylase ( GAD ) isoforms’ expression; (2) arterial pressure ( AP ) and heart rate ( HR ) responses, sympathetic/parasympathetic modulation of heart and vessels and baroreflex sensitivity to GABA A receptor blockade within the PVN . SHR ‐S versus WKY ‐S exhibited higher AP and HR , increased sympathetic reduced parasympathetic modulation, smaller baroreflex sensitivity, and reduced PVN GAD 65 immunoreactivity. SHR ‐T and WKY ‐T showed prompt maintained increase (2–8 weeks) in GAD 65 expression (responsible for GABA vesicular pool synthesis), which occurred simultaneously with HR reduction in SHR ‐T and preceded MAP fall in SHR ‐T and resting bradycardia in WKY ‐T. There was no change in GAD 67 expression (mainly involved with GABA metabolic pool). Resting HR in both groups and basal MAP in SHR were negatively correlated with PVN GAD 65 expression. Normalized baroreflex sensitivity and autonomic control observed only in SHR ‐T were due to recovery of GABA A receptor function into the PVN since bicuculline administration abolished these effects. Data indicated that training augments in both groups the expression/activity of GABA ergic neurotransmission within presympathetic PVN neurons and restores GABA A receptors′ function specifically in the SHR , therefore strengthening GABA ergic modulation of sympathetic outflow in hypertension.