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Brain heterotrimeric Gαi₂-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress.
FASEB J. 2012 Jul; 26(7):2776-87.FJ

Abstract

Fluid and electrolyte homeostasis is integral to blood pressure regulation. However, the central molecular mechanisms regulating the neural control of sodium excretion remain unclear. We have demonstrated that brain Gαi(2)-subunit protein pathways mediate the natriuretic response to α(2)-adrenoreceptor activation in vivo. Consequently, we examined the role of brain Gαi(2) proteins in the neural mechanisms facilitating fluid and electrolyte homeostasis in response to acute [i.v. volume expansion (VE)] or chronic stressful stimuli (dietary sodium restriction vs. supplementation) in conscious Sprague-Dawley rats. Selective oligodeoxynucleotide (ODN)-mediated down-regulation of brain Gαi(2) proteins, but not a scrambled ODN, abolished the renal sympathoinhibitory response and attenuated the natriuresis to VE. In scrambled ODN-treated rats, chronic changes in dietary sodium intake evoked an endogenous, hypothalamic paraventricular nucleus (PVN)-specific, decrease (sodium deficiency) or increase (sodium excess) in PVN Gαi(2) proteins; plasma norepinephrine levels were inversely related to dietary sodium content. Finally, in rats treated with an ODN to prevent high salt-induced up-regulation of brain Gαi(2) proteins, animals exhibited sodium retention, global sympathoexcitation, and elevated blood pressure. Collectively, these data demonstrate that PVN Gαi(2) protein pathways play an endogenous role in maintaining fluid and electrolyte balance by controlling the influence the sympathetic nervous system has on the renal handling of sodium.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics and Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22459149

Citation

Kapusta, Daniel R., et al. "Brain Heterotrimeric Gαi₂-subunit Protein-gated Pathways Mediate Central Sympathoinhibition to Maintain Fluid and Electrolyte Homeostasis During Stress." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 26, no. 7, 2012, pp. 2776-87.
Kapusta DR, Pascale CL, Wainford RD. Brain heterotrimeric Gαi₂-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress. FASEB J. 2012;26(7):2776-87.
Kapusta, D. R., Pascale, C. L., & Wainford, R. D. (2012). Brain heterotrimeric Gαi₂-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 26(7), 2776-87. https://doi.org/10.1096/fj.11-196550
Kapusta DR, Pascale CL, Wainford RD. Brain Heterotrimeric Gαi₂-subunit Protein-gated Pathways Mediate Central Sympathoinhibition to Maintain Fluid and Electrolyte Homeostasis During Stress. FASEB J. 2012;26(7):2776-87. PubMed PMID: 22459149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain heterotrimeric Gαi₂-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress. AU - Kapusta,Daniel R, AU - Pascale,Crissey L, AU - Wainford,Richard D, Y1 - 2012/03/29/ PY - 2012/3/31/entrez PY - 2012/3/31/pubmed PY - 2012/9/21/medline SP - 2776 EP - 87 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 26 IS - 7 N2 - Fluid and electrolyte homeostasis is integral to blood pressure regulation. However, the central molecular mechanisms regulating the neural control of sodium excretion remain unclear. We have demonstrated that brain Gαi(2)-subunit protein pathways mediate the natriuretic response to α(2)-adrenoreceptor activation in vivo. Consequently, we examined the role of brain Gαi(2) proteins in the neural mechanisms facilitating fluid and electrolyte homeostasis in response to acute [i.v. volume expansion (VE)] or chronic stressful stimuli (dietary sodium restriction vs. supplementation) in conscious Sprague-Dawley rats. Selective oligodeoxynucleotide (ODN)-mediated down-regulation of brain Gαi(2) proteins, but not a scrambled ODN, abolished the renal sympathoinhibitory response and attenuated the natriuresis to VE. In scrambled ODN-treated rats, chronic changes in dietary sodium intake evoked an endogenous, hypothalamic paraventricular nucleus (PVN)-specific, decrease (sodium deficiency) or increase (sodium excess) in PVN Gαi(2) proteins; plasma norepinephrine levels were inversely related to dietary sodium content. Finally, in rats treated with an ODN to prevent high salt-induced up-regulation of brain Gαi(2) proteins, animals exhibited sodium retention, global sympathoexcitation, and elevated blood pressure. Collectively, these data demonstrate that PVN Gαi(2) protein pathways play an endogenous role in maintaining fluid and electrolyte balance by controlling the influence the sympathetic nervous system has on the renal handling of sodium. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/22459149/Brain_heterotrimeric_Gαi₂_subunit_protein_gated_pathways_mediate_central_sympathoinhibition_to_maintain_fluid_and_electrolyte_homeostasis_during_stress_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.11-196550?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -