Exercise training improves cardiovascular control in sinoaortic denervated SHR by reducing the elevated angiotensin II and augmenting angiotensin-(1−7) availability within autonomic and neuroendocrine PVN nuclei

Abstract

Previous studies have shown that baroreceptors- and chemoreceptors-denervated SHR exhibit impaired central autonomic circuitry and worsening of the cardiovascular function. It was also known that exercise training (T) ameliorates the autonomic control of the circulation. In the present study we sought to investigate whether sinoaortic denervation (SAD) is able to modify the expression/activity of the renin-angiotensin system (RAS) within brain autonomic areas and the effects induced by T. SHR submitted to SAD or SHAM surgery were trained or kept sedentary (S) for 8 weeks. Femoral artery and vein were chronically cannulated for hemodynamic/autonomic recordings and baroreflex testing (phenylephrine and sodium nitroprusside, i.v). Ang II and Ang (1−7) protein expression (immunofluorescence assays) were quantified within autonomic and neuroendocrine nuclei of the hypothalamic paraventricular nucleus (PVN). SAD-S vs. SHAM-S exhibited large increase in Ang II availability into the ventromedial, dorsal cap and magnocellular PVN nuclei, which are accompanied by augmented sympathetic activity, elevated arterial pressure variability and higher MAP. There was no change in Ang-(1−7) content within these nuclei. In contrast, T largely augmented Ang-(1−7) immunofluorescence in all nuclei, reduced and normalized Ang II availability and ameliorated the autonomic control of the circulation in SAD rats, but did not reduce MAP levels. Data showed that tonic baroreceptors and chemoreceptors’ activity is essential to maintain lower Ang II levels within PVN nuclei. In the absence of afferent signaling, exercise training is still efficient to alter Ang II/Ang-(1−7) balance thus improving cardiovascular control even in the presence of high-pressure levels.