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Central nervous system Gαi2-subunit proteins maintain salt resistance via a renal nerve-dependent sympathoinhibitory pathway.
Hypertension 2013; 61(2):368-75H

Abstract

In salt-resistant phenotypes, chronic elevated dietary sodium intake evokes suppression of renal sodium-retaining mechanisms to maintain sodium homeostasis and normotension. We have recently shown that brain Gαi(2) protein pathways are required to suppress renal sympathetic nerve activity and facilitate maximal sodium excretion during acute intravenous volume expansion in Sprague-Dawley rats. Here, we studied the role of brain Gαi(2) proteins in the endogenous central neural mechanisms acting to maintain fluid and electrolyte homeostasis and normotension during a chronic elevation in dietary salt intake. Naive or bilaterally renal denervated adult male Sprague-Dawley rats were randomly assigned to receive an intracerebroventricular scrambled or Gαi(2) oligodeoxynucleotide infusion and then subjected to either a normal salt (0.4%) or high-salt (8.0%) diet for 21 days. In scrambled oligodeoxynucleotide-infused rats, salt loading, which did not alter blood pressure, evoked a site-specific increase in hypothalamic paraventricular nucleus Gαi(2) protein levels and suppression of circulating norepinephrine content and plasma renin activity. In salt-loaded rats continuously infused intracerebroventricularly with a Gαi(2) oligodeoxynucleotide, animals exhibited sodium and water retention, elevated plasma norepinephrine levels, and hypertension, despite suppression of plasma renin activity. Furthermore, in salt-loaded bilaterally renal denervated rats, Gαi(2) oligodeoxynucleotide infusion failed to evoke salt-sensitive hypertension. Therefore, in salt-resistant rats subjected to a chronic high-salt diet, brain Gαi(2) proteins are required to inhibit central sympathetic outflow to the kidneys and maintain sodium balance and normotension. In conclusion, these data demonstrate a central role of endogenous brain, likely paraventricular nucleus-specific, Gαi(2)-subunit protein-gated signal transduction pathways in maintaining a salt-resistant phenotype.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics and the Whitaker Cardiovascular Institute, Boston University School of Medicine, 72 E Concord St, Boston, MA 02118, USA.No affiliation info availableNo 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

23213191

Citation

Kapusta, Daniel R., et al. "Central Nervous System Gαi2-subunit Proteins Maintain Salt Resistance Via a Renal Nerve-dependent Sympathoinhibitory Pathway." Hypertension (Dallas, Tex. : 1979), vol. 61, no. 2, 2013, pp. 368-75.
Kapusta DR, Pascale CL, Kuwabara JT, et al. Central nervous system Gαi2-subunit proteins maintain salt resistance via a renal nerve-dependent sympathoinhibitory pathway. Hypertension. 2013;61(2):368-75.
Kapusta, D. R., Pascale, C. L., Kuwabara, J. T., & Wainford, R. D. (2013). Central nervous system Gαi2-subunit proteins maintain salt resistance via a renal nerve-dependent sympathoinhibitory pathway. Hypertension (Dallas, Tex. : 1979), 61(2), pp. 368-75. doi:10.1161/HYPERTENSIONAHA.111.00014.
Kapusta DR, et al. Central Nervous System Gαi2-subunit Proteins Maintain Salt Resistance Via a Renal Nerve-dependent Sympathoinhibitory Pathway. Hypertension. 2013;61(2):368-75. PubMed PMID: 23213191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central nervous system Gαi2-subunit proteins maintain salt resistance via a renal nerve-dependent sympathoinhibitory pathway. AU - Kapusta,Daniel R, AU - Pascale,Crissey L, AU - Kuwabara,Jill T, AU - Wainford,Richard D, Y1 - 2012/12/03/ PY - 2012/12/6/entrez PY - 2012/12/6/pubmed PY - 2013/3/21/medline SP - 368 EP - 75 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 61 IS - 2 N2 - In salt-resistant phenotypes, chronic elevated dietary sodium intake evokes suppression of renal sodium-retaining mechanisms to maintain sodium homeostasis and normotension. We have recently shown that brain Gαi(2) protein pathways are required to suppress renal sympathetic nerve activity and facilitate maximal sodium excretion during acute intravenous volume expansion in Sprague-Dawley rats. Here, we studied the role of brain Gαi(2) proteins in the endogenous central neural mechanisms acting to maintain fluid and electrolyte homeostasis and normotension during a chronic elevation in dietary salt intake. Naive or bilaterally renal denervated adult male Sprague-Dawley rats were randomly assigned to receive an intracerebroventricular scrambled or Gαi(2) oligodeoxynucleotide infusion and then subjected to either a normal salt (0.4%) or high-salt (8.0%) diet for 21 days. In scrambled oligodeoxynucleotide-infused rats, salt loading, which did not alter blood pressure, evoked a site-specific increase in hypothalamic paraventricular nucleus Gαi(2) protein levels and suppression of circulating norepinephrine content and plasma renin activity. In salt-loaded rats continuously infused intracerebroventricularly with a Gαi(2) oligodeoxynucleotide, animals exhibited sodium and water retention, elevated plasma norepinephrine levels, and hypertension, despite suppression of plasma renin activity. Furthermore, in salt-loaded bilaterally renal denervated rats, Gαi(2) oligodeoxynucleotide infusion failed to evoke salt-sensitive hypertension. Therefore, in salt-resistant rats subjected to a chronic high-salt diet, brain Gαi(2) proteins are required to inhibit central sympathetic outflow to the kidneys and maintain sodium balance and normotension. In conclusion, these data demonstrate a central role of endogenous brain, likely paraventricular nucleus-specific, Gαi(2)-subunit protein-gated signal transduction pathways in maintaining a salt-resistant phenotype. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/23213191/Central_nervous_system_Gαi2_subunit_proteins_maintain_salt_resistance_via_a_renal_nerve_dependent_sympathoinhibitory_pathway_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.111.00014?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -