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Brain Gαi 2 -subunit proteins and the prevention of salt sensitive hypertension.
Front Physiol 2015; 6:233FP

Abstract

To counter the development of salt-sensitive hypertension, multiple brain G-protein-coupled receptor (GPCR) systems are activated to facilitate sympathoinhibition, sodium homeostasis, and normotension. Currently there is a paucity of knowledge regarding the role of down-stream GPCR-activated Gα-subunit proteins in these critically important physiological regulatory responses required for long-term blood pressure regulation. We have determined that brain Gαi2-proteins mediate natriuretic and sympathoinhibitory responses produced by acute pharmacological (exogenous central nociceptin/orphanin FQ receptor (NOP) and α2-adrenoceptor activation) and physiological challenges to sodium homeostasis (intravenous volume expansion and 1 M sodium load) in conscious Sprague-Dawley rats. We have demonstrated that in salt-resistant rat phenotypes, high dietary salt intake evokes site-specific up-regulation of hypothalamic paraventricular nucleus (PVN) Gαi2-proteins. Further, we established that PVN Gαi2 protein up-regulation prevents the development of renal nerve-dependent sympathetically mediated salt-sensitive hypertension in Sprague-Dawley and Dahl salt-resistant rats. Additionally, failure to up-regulate PVN Gαi2 proteins during high salt-intake contributes to the pathophysiology of Dahl salt-sensitive (DSS) hypertension. Collectively, our data demonstrate that brain, and likely PVN specific, Gαi2 protein pathways represent a central molecular pathway mediating sympathoinhibitory renal-nerve dependent responses evoked to maintain sodium homeostasis and a salt-resistant phenotype. Further, impairment of this endogenous "anti-hypertensive" mechanism contributes to the pathophysiology of salt-sensitive hypertension.

Authors+Show Affiliations

The Department of Pharmacology and Experimental Therapeutics, The Whitaker Cardiovascular Institute, Boston University School of Medicine Boston, MA, USA.The Department of Pharmacology and Experimental Therapeutics, The Whitaker Cardiovascular Institute, Boston University School of Medicine Boston, MA, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

26347659

Citation

Carmichael, Casey Y., and Richard D. Wainford. "Brain Gαi 2 -subunit Proteins and the Prevention of Salt Sensitive Hypertension." Frontiers in Physiology, vol. 6, 2015, p. 233.
Carmichael CY, Wainford RD. Brain Gαi 2 -subunit proteins and the prevention of salt sensitive hypertension. Front Physiol. 2015;6:233.
Carmichael, C. Y., & Wainford, R. D. (2015). Brain Gαi 2 -subunit proteins and the prevention of salt sensitive hypertension. Frontiers in Physiology, 6, p. 233. doi:10.3389/fphys.2015.00233.
Carmichael CY, Wainford RD. Brain Gαi 2 -subunit Proteins and the Prevention of Salt Sensitive Hypertension. Front Physiol. 2015;6:233. PubMed PMID: 26347659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain Gαi 2 -subunit proteins and the prevention of salt sensitive hypertension. AU - Carmichael,Casey Y, AU - Wainford,Richard D, Y1 - 2015/08/19/ PY - 2015/05/29/received PY - 2015/08/03/accepted PY - 2015/9/9/entrez PY - 2015/9/9/pubmed PY - 2015/9/9/medline KW - blood pressure regulation KW - central G-protein coupled receptors KW - central Gαi2 proteins KW - renal sympathetic nerves KW - salt-sensitive hypertension KW - sodium homeostasis KW - sympathetic nervous system SP - 233 EP - 233 JF - Frontiers in physiology JO - Front Physiol VL - 6 N2 - To counter the development of salt-sensitive hypertension, multiple brain G-protein-coupled receptor (GPCR) systems are activated to facilitate sympathoinhibition, sodium homeostasis, and normotension. Currently there is a paucity of knowledge regarding the role of down-stream GPCR-activated Gα-subunit proteins in these critically important physiological regulatory responses required for long-term blood pressure regulation. We have determined that brain Gαi2-proteins mediate natriuretic and sympathoinhibitory responses produced by acute pharmacological (exogenous central nociceptin/orphanin FQ receptor (NOP) and α2-adrenoceptor activation) and physiological challenges to sodium homeostasis (intravenous volume expansion and 1 M sodium load) in conscious Sprague-Dawley rats. We have demonstrated that in salt-resistant rat phenotypes, high dietary salt intake evokes site-specific up-regulation of hypothalamic paraventricular nucleus (PVN) Gαi2-proteins. Further, we established that PVN Gαi2 protein up-regulation prevents the development of renal nerve-dependent sympathetically mediated salt-sensitive hypertension in Sprague-Dawley and Dahl salt-resistant rats. Additionally, failure to up-regulate PVN Gαi2 proteins during high salt-intake contributes to the pathophysiology of Dahl salt-sensitive (DSS) hypertension. Collectively, our data demonstrate that brain, and likely PVN specific, Gαi2 protein pathways represent a central molecular pathway mediating sympathoinhibitory renal-nerve dependent responses evoked to maintain sodium homeostasis and a salt-resistant phenotype. Further, impairment of this endogenous "anti-hypertensive" mechanism contributes to the pathophysiology of salt-sensitive hypertension. SN - 1664-042X UR - https://www.unboundmedicine.com/medline/citation/26347659/Brain_Gαi_2__subunit_proteins_and_the_prevention_of_salt_sensitive_hypertension_ L2 - https://dx.doi.org/10.3389/fphys.2015.00233 DB - PRIME DP - Unbound Medicine ER -