Abstract
Renal sensory activity is centrally integrated within brain nuclei involved in the control of cardiovascular function, suggesting that renal afferents regulate basal and reflex sympathetic vasomotor activity. Evidence has shown that renal deafferentation (DAx) evokes a hypotensive and sympathoinhibitory effect in experimental models of cardiovascular diseases; however, the underlying mechanisms involved in this phenomenon need to be clarified, especially those related to central aspects. We aimed to investigate the role of renal afferents in the control of γ-aminobutyric acid (GABA)ergic inputs to the paraventricular nucleus (PVN) of the hypothalamus in renovascular hypertensive (2K1C) rats and their influence in the regulation of cardiovascular function. Hypertension was induced by clipping the left renal artery. After 4 weeks, renal DAx was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of DAx, microinjection of muscimol into the PVN was performed in order to evaluate the influence of GABAergic activity in the PVN and its contribution to the control of renal sympathetic nerve activity (rSNA) and blood pressure (BP). Muscimol microinjected into the PVN triggered a higher drop in BP and rSNA in the 2K1C rats and renal DAx mitigated these responses. These results suggest that renal afferents are involved in the GABAergic changes found in the PVN of 2K1C rats. Although the functional significance of this phenomenon needs to be clarified, it is reasonable to speculate that GABAergic alterations occur to mitigate microglia activation-induced sympathoexcitation in the PVN of 2K1C rats.
Highlights
Elevated sympathetic vasomotor activity is implicated in cardiovascular diseases, either experimentally or clinically (Grassi, 2010; Campos et al, 2015)
The main findings of this study demonstrate that changes in renal sensory activity in 2K1C rats evoke an increase in the GABAergic inputs into the paraventricular nucleus (PVN) and contribute to impaired cardiac baroreflex sensitivity
It has been shown that rostral ventrolateral medulla (RVLM) is an important site integrating renal afferent signaling (Nishi et al, 2017), glutamatergic neurons in the PVN that project into RVLM are activated by stimulation of renal afferents (Xu et al, 2015)
Summary
Elevated sympathetic vasomotor activity is implicated in cardiovascular diseases, either experimentally or clinically (Grassi, 2010; Campos et al, 2015). Central Effects of Renal Deafferentation benefits occur have been extensively studied in recent years, especially how the central nervous system (CNS) drives sympathetic vasomotor overactivation in pathophysiological conditions (Oliveira-Sales et al, 2009; Nishi et al, 2019) It is well-described that phenotypic changes in brain nuclei involved in cardiovascular control contribute to the maintenance of high sympathetic outflow in cardiovascular diseases, such as hypertension or heart failure (Oliveira-Sales et al, 2009; Carillo et al, 2012; Milanez et al, 2020). It is not fully known what leads sympathetic activation in cardiovascular diseases, recent studies highlight the role of sensory signaling in these alterations, especially the renal sensory system (Nishihara et al, 2017; Zheng et al, 2018)
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