Afferent innervation of the ischemic kidney contributes to renal dysfunction in renovascular hypertensive rats

Lopes, Nathalia R.; Milanez, Maycon I.O.; Martins, Beatriz; Veiga, Amanda C; Ferreira, Giovanna R.; Gomes, Guiomar Nascimento; Girardi, Adriana C. C.; Carvalho, Polliane Morais de; Nogueira, Fernando; Campos, Rui; Bergamaschi, Cássia Toledo; Nishi, Érika E.

doi:10.1007/s00424-019-02346-4

Cited by 34 publications

(27 citation statements)

References 31 publications

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“…Thus, considering that we previously reported a robust renal sympathoinhibitory effect caused by DAx in the 2K1C rats (Lopes et al, 2020), we hypothesized in the present study that this phenomenon may be triggered by alterations in the GABAergic inputs into the PVN of 2K1C DAx rats. In addition, in order to analyze the effects of DAx in terms of sympathetic vasomotor activity reflex control, we evaluated the cardiac baroreflex sensitivity in the presence and absence of renal sensory activity in 2K1C rats.…”

Section: Introductionmentioning

confidence: 63%

“…In the sham groups, rats underwent the same surgical procedure described above, but with vehicle application (0.1% ethanol and 0.1% Tween 80) around the renal artery (Foss et al, 2015). As previously shown in another study by our group, the confirmation of DAx was verified by the reduction in calcitonin gene-related peptide (CGRP) expression by immunohistochemical analysis in the renal pelvis after 2 weeks of the procedure (Lopes et al, 2020) when all data were collected. Two independent sets of experiments were performed: one set for BP and rSNA responses triggered by muscimol, an agonist of GABA-A receptors, microinjected into PVN and another set for analysis of cardiac baroreflex sensitivity in conscious rats and microglia activation analysis in the PVN.…”

Section: Animals and Experimental Protocolmentioning

confidence: 95%

“…Elevated sympathetic vasomotor activity is implicated in cardiovascular diseases, either experimentally or clinically (Grassi, 2010;Campos et al, 2015). Studies indicate that approaches aimed at reducing sympathetic vasomotor tone are beneficial in these conditions (Nishi et al, 2019;Lopes et al, 2020;Veiga et al, 2020); therefore, the underlying mechanisms by which such 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).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, it is possible to study the selective role of sensory renal afferents and evaluate the effects evoked by their removal in the course of the disease (Foss et al, 2015). For example, we recently showed that the selective renal nerve deafferentation (DAx) causes a decrease in blood pressure (BP) and renal sympathetic nerve activity (rSNA) in the Goldblatt 2K1C rats and 5/6 nephrectomy model of chronic renal failure, indicating that the renal sensory afferents are centrally integrated and trigger changes in central nuclei involved in the control of cardiovascular function (Lopes et al, 2020;Veiga et al, 2020). In fact, evidences indicate that brain nuclei involved in the cardiovascular control, such as the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus (PVN) of the hypothalamus, receive projections of sensory renal afferents (Nishi et al, 2017;Zheng and Patel, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Renal Sensory Activity Regulates the γ-Aminobutyric Acidergic Inputs to the Paraventricular Nucleus of the Hypothalamus in Goldblatt Hypertension

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 63%

Section: Animals and Experimental Protocolmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Renal Sensory Activity Regulates the γ-Aminobutyric Acidergic Inputs to the Paraventricular Nucleus of the Hypothalamus in Goldblatt Hypertension

et al. 2020

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“…In their elegant study, Lopes and colleagues [6] described that chemical afferent renal denervation (ARD) decreased blood pressure (BP), renal sympathetic nerve activity (rSNA) and reactive oxygen species (ROS) in both kidneys and normalized renal function, proteinuria and activation of intrarenal renin-angiotensin system (RAS) in renovascular hypertensive animals. These data demonstrate that afferent renal nerves are crucial for the maintenance of BP and renal sympathetic hyperactivation, as well as renal function, in the renovascular hypertension model [6].…”

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confidence: 99%