Abstract
Exercise training has profound effects on the renin-angiotensin system, inflammatory cytokines and oxidative stress, all of which affect autonomic nervous system activity and regulate blood pressure (BP) in both physiological and pathophysiological states. Using the Induction-Delay-Expression paradigm, our previous studies demonstrated that various challenges (stressors) during Induction resulted in hypertensive response sensitization (HTRS) during Expression. The present study tested whether voluntary exercise would protect against subpressor angiotensin (ANG) II-induced HTRS in rats. Adult male rats were given access to either “blocked” (sedentary rats) or functional running (exercise rats) wheels for 12 weeks, and the Induction-Delay-Expression paradigm was applied for the rats during the last 4 weeks. A subpressor dose of ANG II given during Induction produced an enhanced hypertensive response to a pressor dose of ANG II given during Expression in sedentary rats in comparison to sedentary animals that received saline (vehicle control) during Induction. Voluntary exercise did not attenuate the pressor dose of ANG II-induced hypertension but prevented the expression of HTRS seen in sedentary animals. Moreover, voluntary exercise reduced body weight gain and feed efficiency, abolished the augmented BP reduction after ganglionic blockade, reversed the increased mRNA expression of pro-hypertensive components, and upregulated mRNA expression of antihypertensive components in the lamina terminalis and hypothalamic paraventricular nucleus, two key brain nuclei involved in the control of sympathetic activity and BP regulation. These results indicate that exercise training plays a beneficial role in preventing HTRS and that this is associated with shifting the balance of the brain prohypertensive and antihypertensive pathways in favor of attenuated central activity driving sympathetic outflow and reduced BP.
Highlights
Hypertension is major risk for cardiovascular disease affecting more than 31% adults worldwide
We found that voluntary exercise normalized the subpressor dose of ANG II-induced upregulation of mRNA expression of several reninangiotensin system (RAS) components and proinflammatory cytokines (PICs) and NADPH oxidase in the LT and paraventricular nucleus (PVN) and that these were accompanied by the abolition of hypertensive response sensitization (HTRS) and attenuation of increased sympathetic tone
It has been demonstrated that long-term exercise training can upregulate IL-10, ACE2, and Mas-R expression in the brain of spontaneously hypertensive rats (SHRs) and heart failure models (Agarwal et al, 2011; Zucker et al, 2015). Consistent with these previous studies, we found in the present study that exercise training upregulated the mRNA expression of antihypertensive components including IL-10, AT2-R, and Mas-R in the LT and PVN of sedentary animals and induced an enhanced mRNA expression of these antihypertensive components in the LT in rats pretreated with the subpressor dose of ANG II
Summary
Hypertension is major risk for cardiovascular disease affecting more than 31% adults worldwide. The activation of the sympathetic nervous system (SNS) is a major mechanism both in human high blood pressure and in several models of hypertension in animals (DiBona, 2013; Dampney, 2016; Haspula and Clark, 2018; Johnson and Xue, 2018). In this regard, activation of reninangiotensin system (RAS) and elevation of inflammation and oxidative stress in the central nervous system (CNS) produce a state of sympathetic overactivity that plays an essential role in the onset and development of hypertension (Peterson et al, 2006; Kalupahana and Moustaid-Moussa, 2012; Huber et al, 2017; Haspula and Clark, 2018). The PVN integrates this information and sends projections either to the rostral ventrolateral medulla (RVLM) or to the spinal cord intermediolateral cell column to exaggerate sympathetic outflow and elevate BP under the pathophysiological state of hypertension (Johnson and Gross, 1993; Mimee et al, 2013; Dampney, 2016; Sharma et al, 2021)
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