Intrarenal ghrelin receptor inhibition ameliorates angiotensin ii-dependent hypertension in rats.

INTRARENAL GHRELIN RECEPTOR INHIBITION AMELIORATES ANGIOTENSIN II-DEPENDENT HYPERTENSION IN RATS.
Am J Physiol Renal Physiol. 2018 Jun 20;:
Authors: Kemp BA, Howell NL, Padia SH
Abstract
The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Rats also received intrarenal infusion of vehicle, GR siRNA, or scrambled (SCR) siRNA. In rats receiving intrarenal vehicle or intrarenal SCR siRNA, systemic Angiotensin II infusion increased sodium retention and BP on day 1, and BP remained elevated throughout the 5-day study. These rats also demonstrated increased CD GR expression after 5 days of infusion. However, intrarenal GR siRNA infusion prevented Angiotensin II-mediated sodium retention on day 1, induced a continuously negative cumulative sodium balance compared with Angiotensin II alone, and reduced BP chronically. Glomerular filtration rate and renal blood flow remained unchanged in GR siRNA-infused rats. Systemic Angiotensin II infusion also increased serum aldosterone levels, CD αENaC and pS...

Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: Kemp BA, Howell NL, Padia SH Tags: Am J Physiol Renal Physiol Source Type: research