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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/R535    most recent 00043.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wainford, R. D. Articles by Kapusta, D. R. PubMed PubMed Citation Articles by Wainford, R. D. Articles by Kapusta, D. R.

HEMODYNAMICS AND CARDIORENAL INTEGRATION

Central G-alpha subunit protein-mediated control of cardiovascular function, urine output, and vasopressin secretion in conscious Sprague-Dawley rats

¹Department of Pharmacology and ²Anesthesiology and the Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Submitted 21 January 2008 ; accepted in final form 3 June 2008

The role(s) of central G-proteins in the regulation of cardiovascular and renal function is unknown. We examined how inhibition/downregulation of central Gi/Go, Gz or Gq proteins altered the characteristic cardiovascular (depressor), renal excretory (diuretic), and plasma AVP (inhibitory) responses to intracerebroventricular injection of nociceptin/orphanin FQ (N/OFQ) in rats. Before investigation, rats were pretreated intracerebroventricularly with saline vehicle (5 µl, 48 h, n = 6), pertussis toxin (PTX; 48-h, 1 µg, n = 6), or Gz, Gq, or scrambled oligodeoxynucleotide (ODN) (25 µg, 24 h, n = 6 per group). On the study day, intracerebroventricular N/OFQ (5.5 nmol) or vehicle (5 µl) was injected into pretreated conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were recorded, and urine was collected for 90 min. In vehicle or scrambled ODN groups, intracerebroventricular N/OFQ decreased MAP and HR and produced water diuresis (sensitive to UFP-101, N/OFQ receptor antagonist). The hypotension and bradycardia, but not diuresis, to N/OFQ were abolished in PTX-pretreated rats. In contrast, intracerebroventricular ODN pretreatment markedly blunted (Gz) or augmented (Gq) the diuresis to intracerebroventricular N/OFQ. In separate studies, the action of central N/OFQ to decrease plasma AVP levels in naïve water-restricted rats was differentially altered by intracerebroventricular Gz ODN (blunted) and Gq ODN (augmented) pretreatment. These studies demonstrate central Gi/Go activity mediates intracerebroventricular N/OFQ's cardiovascular depressor function. Alternatively, central Gz (inhibitory) and Gq (stimulatory) activity differentially modulates AVP release to control the pattern of diuresis to intracerebroventricular N/OFQ. These findings highlight the novel selective central G-subunit protein-mediated control of cardiovascular vs. renal excretory function.

central G-subunit proteins; central nervous system; cardiovascular and renal excretory function; vasopressin/antidiuretic hormone; nociceptin/orphanin FQ