Sensory Afferent Renal Nerve Activated Gαi 2 Subunit Proteins Mediate the Natriuretic, Sympathoinhibitory and Normotensive Responses to Peripheral Sodium Challenges.

Autor: Moreira JD; Whitaker Cardiovascular Institute, School of Medicine, Boston University, Boston, MA, United States.; Department of Medicine, School of Medicine, Boston University, Boston, MA, United States., Nist KM; Whitaker Cardiovascular Institute, School of Medicine, Boston University, Boston, MA, United States.; Department of Anatomy & Neurobiology, School of Medicine, Boston University, Boston, MA, United States., Carmichael CY; Whitaker Cardiovascular Institute, School of Medicine, Boston University, Boston, MA, United States.; Department of Pharmacology and Experimental Therapeutics, School of Medicine, Boston University, Boston, MA, United States., Kuwabara JT; Whitaker Cardiovascular Institute, School of Medicine, Boston University, Boston, MA, United States.; Department of Pharmacology and Experimental Therapeutics, School of Medicine, Boston University, Boston, MA, United States., Wainford RD; Whitaker Cardiovascular Institute, School of Medicine, Boston University, Boston, MA, United States.; Department of Pharmacology and Experimental Therapeutics, School of Medicine, Boston University, Boston, MA, United States.
Jazyk: angličtina
Zdroj: Frontiers in physiology [Front Physiol] 2021 Nov 30; Vol. 12, pp. 771167. Date of Electronic Publication: 2021 Nov 30 (Print Publication: 2021).
DOI: 10.3389/fphys.2021.771167
Abstrakt: We have previously reported that brain Gαi 2 subunit proteins are required to maintain sodium homeostasis and are endogenously upregulated in the hypothalamic paraventricular nucleus (PVN) in response to increased dietary salt intake to maintain a salt resistant phenotype in rats. However, the origin of the signal that drives the endogenous activation and up-regulation of PVN Gαi 2 subunit protein signal transduction pathways is unknown. By central oligodeoxynucleotide (ODN) administration we show that the pressor responses to central acute administration and central infusion of sodium chloride occur independently of brain Gαi 2 protein pathways. In response to an acute volume expansion, we demonstrate, via the use of selective afferent renal denervation (ADNX) and anteroventral third ventricle (AV3V) lesions, that the sensory afferent renal nerves, but not the sodium sensitive AV3V region, are mechanistically involved in Gαi 2 protein mediated natriuresis to an acute volume expansion [peak natriuresis (μeq/min) sham AV3V: 43 ± 4 vs. AV3V 45 ± 4 vs. AV3V + Gαi 2 ODN 25 ± 4, p < 0.05; sham ADNX: 43 ± 4 vs. ADNX 23 ± 6, AV3V + Gαi 2 ODN 25 ± 3, p < 0.05]. Furthermore, in response to chronically elevated dietary sodium intake, endogenous up-regulation of PVN specific Gαi 2 proteins does not involve the AV3V region and is mediated by the sensory afferent renal nerves to counter the development of the salt sensitivity of blood pressure (MAP [mmHg] 4% NaCl; Sham ADNX 124 ± 4 vs. ADNX 145 ± 4, p < 0.05; Sham AV3V 125 ± 4 vs. AV3V 121 ± 5). Additionally, the development of the salt sensitivity of blood pressure following central ODN-mediated Gαi 2 protein down-regulation occurs independently of the actions of the brain angiotensin II type 1 receptor. Collectively, our data suggest that in response to alterations in whole body sodium the peripheral sensory afferent renal nerves, but not the central AV3V sodium sensitive region, evoke the up-regulation and activation of PVN Gαi 2 protein gated pathways to maintain a salt resistant phenotype. As such, both the sensory afferent renal nerves and PVN Gαi 2 protein gated pathways, represent potential targets for the treatment of the salt sensitivity of blood pressure.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Moreira, Nist, Carmichael, Kuwabara and Wainford.)
Databáze: MEDLINE
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