NOS1-dependent negative feedback regulation of the epithelial sodium channel in the collecting duct.

NOS1-dependent negative feedback regulation of the epithelial sodium channel in the collecting duct. Am J Physiol Renal Physiol. 2014 Nov 12;:ajprenal.00596.2013 Authors: Hyndman KA, Bugaj V, Mironova E, Stockand JD, Pollock JS Abstract With an increase in urine flow there is a significant increase in shear stress against the renal epithelium including the inner medullary collecting duct (IMCD), resulting in an increase in nitric oxide (NO) production. The mechanisms of the shear stress mediated increases in NO are undetermined. Previous studies found that shear stress increases ENaC open probability and ET-1 production in an ENaC dependent mechanism in the collecting duct (CD). Given that ET-1 stimulates NO production in the CD, we hypothesized that shear stress-induced NO production is downstream of shear stress-induced ENaC activation and ET-1 production in a negative feedback loop. We determined that NOS1 and NOS3 contribute to shear stress mediated NO production in the CD, that is attenuated by low doses of the ENaC inhibitors, amiloride and benzamil. Moreover, ETB receptor blockade significantly blunted the shear stress-mediated NO production. We further elucidated if mice lacking NOS1 in the collecting duct (CDNOS1KO) have an impaired renal ET-1 system in the CD. Although urinary ET-1 production and inner medullary ET receptor expression was similar between flox control and CDNOS1KO mice, acute ET-1 treatment significantly red...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research