We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (∼9% in WKY and SHR) and MAP reductions (−8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (−13%) and arteriolar wall/lumen ratio (−35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.

Michelini LC. Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity. Am J Physiol Regul Integr Comp Physiol 301: R958 -R966, 2011. First published July 27, 2011 doi:10.1152/ajpregu.00104.2011.-We showed previously that oxytocinergic (OTergic) projections from the hypothalamic paraventricular nucleus (PVN) to the dorsal brain stem mediate traininginduced heart rate (HR) adjustments and that beneficial effects of training are blocked by sinoaortic denervation (SAD; Exp Physiol 94: 630 -640; 1103-1113). We sought now to determine the combined effect of training and SAD on PVN OTergic neurons in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats underwent SAD or sham surgery and were trained (55% of maximal capacity) or kept sedentary for 3 mo. After hemodynamic measurements were taken at rest, rats were deeply anesthetized. Fresh brains were frozen and sliced to isolate the PVN; samples were processed for OT expression (real-time PCR) and fixed brains were processed for OT immunofluorescence. In sham rats, training improved treadmill performance and increased the gain of baroreflex control of HR. Training reduced resting HR (Ϫ8%) in both groups, with a fall in blood pressure (Ϫ10%) only in SHR rats. These changes were accompanied by marked increases in PVN OT mRNA expression (3.9-and 2.2-fold in WKY and SHR rats, respectively) and peptide density in PVN OTergic neurons (2.6-fold in both groups), with significant correlations between OT content and training-induced resting bradycardia. SAD abolished PVN OT mRNA expression and markedly reduced PVN OT density in WKY and SHR. Training had no effect on HR, PVN OT mRNA, or OT content following SAD. The chronic absence of inputs from baroreceptors and chemoreceptors uncovers the pivotal role of afferent signaling in driving both the plasticity and activity of PVN OTergic neurons, as well as the beneficial effects of training on cardiovascular control. sinoaortic denervation; exercise training; hypothalamus; paraventricular nucleus; supraoptic nucleus; oxytocin; spontaneous hypertension ACCUMULATING EXPERIMENTAL evidence from our and other laboratories has shown that aerobic training promotes several beneficial cardiovascular effects in normotensive and hypertensive individuals. Training causes remodeling of the heart with a simultaneous stroke volume increase and heart rate (HR) decrease (5, 34, 40), outward eutrophic remodeling of arterioles, capillary angiogenesis, and venule neoformation in the exercised muscles (1-3, 10, 24). Exercise training is also accompanied by a predominance of relaxation over contractile endothelium-derived factors (15, 44). These adaptive mechanisms by improving blood flow and tissue conductance, by reducing vascular resistance, and restoring normal endothelial function favor the amelioration of impaired functions in cardiovascular disease.Training reduces both the activity of the renin-angiotensin system and oxidative stress (13,22,38) and effectively induces neuronal pla...

The blood-brain barrier (BBB) is a complex multicellular structure acting as selective barrier controlling the transport of substances between these compartments. Accumulating evidence has shown that chronic hypertension is accompanied by BBB dysfunction, deficient local perfusion and plasma angiotensin II (Ang II) access into the parenchyma of brain areas related to autonomic circulatory control. Knowing that spontaneously hypertensive rats (SHR) exhibit deficient autonomic control and brain Ang II hyperactivity and that exercise training is highly effective in correcting both, we hypothesized that training, by reducing Ang II content, could improve BBB function within autonomic brain areas of the SHR. After confirming the absence of BBB lesion in the pre-hypertensive SHR, but marked fluorescein isothiocyanate dextran (FITC, 10 kD) leakage into the brain parenchyma of the hypothalamic paraventricular nucleus (PVN), nucleus of the solitary tract, and rostral ventrolateral medulla during the established phase of hypertension, adult SHR, and age-matched WKY were submitted to a treadmill training (T) or kept sedentary (S) for 8 weeks. The robust FITC leakage within autonomic areas of the SHR-S was largely reduced and almost normalized since the 2nd week of training (T2). BBB leakage reduction occurred simultaneously and showed strong correlations with both decreased LF/HF ratio to the heart and reduced vasomotor sympathetic activity (power spectral analysis), these effects preceding the appearance of resting bradycardia (T4) and partial pressure fall (T8). In other groups of SHR-T simultaneously infused with icv Ang II or saline (osmotic mini-pumps connected to a lateral ventricle cannula) we proved that decreased local availability of this peptide and reduced microglia activation (IBA1 staining) are crucial mechanisms conditioning the restoration of BBB integrity. Our data also revealed that Ang II-induced BBB lesion was faster within the PVN (T2), suggesting the prominent role of this nucleus in driven hypertension-induced deficits. These original set of data suggest that reduced local Ang II content (and decreased activation of its downstream pathways) is an essential and early-activated mechanism to maintain BBB integrity in trained SHR and uncovers a novel beneficial effect of exercise training to improve autonomic control even in the presence of hypertension.

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.