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Hypothalamic paraventricular nucleus G alpha q subunit protein pathways mediate vasopressin dysregulation and fluid retention in salt-sensitive rats.
Endocrinology 2010; 151(11):5403-14E

Abstract

Central Gαz and Gαq protein-gated pathways play a pivotal role in modulating (inhibiting vs. stimulating, respectively) vasopressin release and urine output; these studies examined the role of brain Gαz/Gαq proteins in the regulation of vasopressin secretion during high-salt challenge. We examined the effects of 21-d normal or high salt intake on plasma vasopressin levels, daily sodium and water balance, and brain Gαz and Gαq protein levels in male Sprague-Dawley (SD), Dahl salt-resistant (DSR), and Dahl salt-sensitive (DSS) rats. Additionally, the effect of central Gαq protein down-regulation on these parameters and the diuretic response evoked by pharmacological [nociceptin/orphanin FQ; 5.5 nmol intracerebroventricularly (icv)] and physiological stimuli (isotonic-saline volume expansion, 5% bodyweight, iv) was examined. After 21 d of high salt intake, DSS, but not SD or DSR rats, exhibited vasopressin dysregulation, as evidenced by elevated plasma vasopressin levels (P < 0.05), marked positive water (and sodium) balance (P < 0.05), and an impaired diuretic response to pharmacological and physiological stimuli (P < 0.05). Chronic high salt intake (21 d) evoked down-regulation of Gαq (P < 0.05), but not Gαz, proteins in the hypothalamic paraventricular nucleus of SD and DSR, but not DSS rats. In salt-challenged (21 d) DSS rats, acute oligodeoxynucleotide-mediated down-regulation of central Gαq proteins returned plasma vasopressin to control levels (P < 0.05), decreased salt-induced water retention (P < 0.05), and restored the profound diuretic responses to pharmacological and physiological stimuli (P < 0.05). Therefore, the down-regulation of PVN Gαq proteins plays a critical counter-regulatory role in preventing vasopressin hypersecretion in salt-resistant phenotypes and may represent a new therapeutic target in pathophysiological states featuring vasopressin dysregulation.

Authors+Show Affiliations

Department of Pharmacology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, Louisiana 70112, USA. rwainf@lsuhsc.eduNo 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

20861238

Citation

Wainford, Richard D., and Daniel R. Kapusta. "Hypothalamic Paraventricular Nucleus G Alpha Q Subunit Protein Pathways Mediate Vasopressin Dysregulation and Fluid Retention in Salt-sensitive Rats." Endocrinology, vol. 151, no. 11, 2010, pp. 5403-14.
Wainford RD, Kapusta DR. Hypothalamic paraventricular nucleus G alpha q subunit protein pathways mediate vasopressin dysregulation and fluid retention in salt-sensitive rats. Endocrinology. 2010;151(11):5403-14.
Wainford, R. D., & Kapusta, D. R. (2010). Hypothalamic paraventricular nucleus G alpha q subunit protein pathways mediate vasopressin dysregulation and fluid retention in salt-sensitive rats. Endocrinology, 151(11), pp. 5403-14. doi:10.1210/en.2010-0345.
Wainford RD, Kapusta DR. Hypothalamic Paraventricular Nucleus G Alpha Q Subunit Protein Pathways Mediate Vasopressin Dysregulation and Fluid Retention in Salt-sensitive Rats. Endocrinology. 2010;151(11):5403-14. PubMed PMID: 20861238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypothalamic paraventricular nucleus G alpha q subunit protein pathways mediate vasopressin dysregulation and fluid retention in salt-sensitive rats. AU - Wainford,Richard D, AU - Kapusta,Daniel R, Y1 - 2010/09/22/ PY - 2010/9/24/entrez PY - 2010/9/24/pubmed PY - 2010/11/5/medline SP - 5403 EP - 14 JF - Endocrinology JO - Endocrinology VL - 151 IS - 11 N2 - Central Gαz and Gαq protein-gated pathways play a pivotal role in modulating (inhibiting vs. stimulating, respectively) vasopressin release and urine output; these studies examined the role of brain Gαz/Gαq proteins in the regulation of vasopressin secretion during high-salt challenge. We examined the effects of 21-d normal or high salt intake on plasma vasopressin levels, daily sodium and water balance, and brain Gαz and Gαq protein levels in male Sprague-Dawley (SD), Dahl salt-resistant (DSR), and Dahl salt-sensitive (DSS) rats. Additionally, the effect of central Gαq protein down-regulation on these parameters and the diuretic response evoked by pharmacological [nociceptin/orphanin FQ; 5.5 nmol intracerebroventricularly (icv)] and physiological stimuli (isotonic-saline volume expansion, 5% bodyweight, iv) was examined. After 21 d of high salt intake, DSS, but not SD or DSR rats, exhibited vasopressin dysregulation, as evidenced by elevated plasma vasopressin levels (P < 0.05), marked positive water (and sodium) balance (P < 0.05), and an impaired diuretic response to pharmacological and physiological stimuli (P < 0.05). Chronic high salt intake (21 d) evoked down-regulation of Gαq (P < 0.05), but not Gαz, proteins in the hypothalamic paraventricular nucleus of SD and DSR, but not DSS rats. In salt-challenged (21 d) DSS rats, acute oligodeoxynucleotide-mediated down-regulation of central Gαq proteins returned plasma vasopressin to control levels (P < 0.05), decreased salt-induced water retention (P < 0.05), and restored the profound diuretic responses to pharmacological and physiological stimuli (P < 0.05). Therefore, the down-regulation of PVN Gαq proteins plays a critical counter-regulatory role in preventing vasopressin hypersecretion in salt-resistant phenotypes and may represent a new therapeutic target in pathophysiological states featuring vasopressin dysregulation. SN - 1945-7170 UR - https://www.unboundmedicine.com/medline/citation/20861238/Hypothalamic_paraventricular_nucleus_G_alpha_q_subunit_protein_pathways_mediate_vasopressin_dysregulation_and_fluid_retention_in_salt_sensitive_rats_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2010-0345 DB - PRIME DP - Unbound Medicine ER -