These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


PUBMED FOR HANDHELDS

Search MEDLINE/PubMed


  • Title: Hypothalamic paraventricular nucleus G alpha q subunit protein pathways mediate vasopressin dysregulation and fluid retention in salt-sensitive rats.
    Author: Wainford RD, Kapusta DR.
    Journal: Endocrinology; 2010 Nov; 151(11):5403-14. PubMed ID: 20861238.
    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.
    [Abstract] [Full Text] [Related] [New Search]