Role of soluble guanylate cyclase in renal hemodynamics and autoregulation in the rat.

Abstract

We studied the influence of soluble guanylate (sGC) on renal blood flow (RBF), glomerular filtration rate (GFR), and RBF autoregulation and its role in mediating the hemodynamic effects of endogenous nitric oxide (NO). Arterial pressure (AP), heart rate (HR), RBF, GFR, urine flow (UV), and the efficiency and mechanisms of RBF autoregulation were studied in anesthetized rats during intravenous infusion of sGC activator cinaciguat before and (except GFR) also after inhibition of NO synthase (NOS) by Nω-nitro-L-arginine methyl ester. Cinaciguat (0.1, 0.3, 1, 3, 10 μg·kg(-1)·min(-1), n=7) reduced AP and increased HR, but did not significantly alter RBF. In clearance experiments (FITC-sinistrin, n=7) GFR was not significantly altered by cinaciguat (0.1 and 1 μg·kg(-1)·min(-1)), but RBF slightly rose (+12%) and filtration fraction (FF) fell (-23%). RBF autoregulatory efficiency (67 vs. 104%) and myogenic response (33 vs. 44 units) were slightly depressed (n=9). NOS inhibition (n=7) increased AP (+38 mmHg), reduced RBF (-53%), and greatly augmented the myogenic response in RBF autoregulation (97 vs. 35 units), attenuating the other regulatory mechanisms. These changes were reversed by 77, 78, and 90% by 1 μg·kg(-1)·min(-1) cinaciguat. In vehicle controls (n=3), in which cinaciguat-induced hypotension was mimicked by aortic compression, the NOS inhibition-induced changes were not affected. We conclude that sGC activation leaves RBF and GFR well maintained despite hypotension and only slightly impairs autoregulation. The ability to largely normalize AP, RBF, RBF autoregulation, and renovascular myogenic response after NOS inhibition indicates that these hemodynamic effects of NO are predominantly mediated via sGC.

• Authors: Marcel Dautzenberg, Antje Kahnert, Johannes-Peter Stasch, Armin Just
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 307 Issue 9 Pg. F1003-12 (Nov 01 2014) ISSN: 1522-1466 [Electronic] United States
• PMID: 25209860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Benzoates
• Receptors, Cytoplasmic and Nuclear
• Nitric Oxide
• BAY 58-2667
• Guanylate Cyclase
• Soluble Guanylyl Cyclase

Topics

• Animals
• Benzoates (pharmacology)
• Glomerular Filtration Rate (drug effects)
• Guanylate Cyclase (physiology)
• Male
• Nitric Oxide (physiology)
• Rats
• Rats, Wistar
• Receptors, Cytoplasmic and Nuclear (physiology)
• Renal Circulation (drug effects, physiology)
• Soluble Guanylyl Cyclase