CALL FOR PAPERS Renal Hemodynamics: Integrating with the Nephron and Beyond Role of soluble guanylate cyclase in renal hemodynamics and autoregulation in the rat

Dautzenberg M, Kahnert A, Stasch JP, Just A. Role of soluble guanylate cyclase in renal hemodynamics and autoregulation in the rat. Am J Physiol Renal Physiol 307: F1003–F1012, 2014. First published September 10, 2014; doi:10.1152/ajprenal.00229.2014.—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 N -nitro-L-arginine methyl ester. Cinaciguat (0.1, 0.3, 1, 3, 10 g·kg ·min , 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 g·kg ·min ), 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 g·kg ·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.