Regulation of renin gene expression in kidneys of eNOS- and nNOS-deficient mice

Abstract

Our study aimed to assess the roles of nitric oxide derived from endothelium NO-synthase (eNOS) and macula densa neuronal NO-synthase (nNOS) in the regulation of renal renin expression. For this purpose renin mRNA levels and renin content were determined in kidneys of wild-type (wt), nNOS-deficient (nNOS–/–), and eNOS-deficient (eNOS–/–) mice, in which the renin system was suppressed by feeding a high-salt diet (NaCl 4%), or was stimulated by feeding a low-salt (NaCl 0.02%) diet together with the converting-enzyme inhibitor ramipril (10 mg kg –1 day –1 ). In all mouse strains, renin mRNA levels were inversely related to the rate of sodium intake. In eNOS–/– mice renin mRNA levels and renal renin content were 50% lower than in wt mice at each level of salt intake, whilst in nNOS–/– mice renin expression was not different from wt controls. Administration of the general NO-synthase inhibitor nitro- l -arginine methyl ester ( l -NAME, 50 mg kg –1 day –1 ) to mice kept on the low-salt/ramipril regimen caused a decrease of renal renin mRNA levels in wt and nNOS–/– mice, but not in eNOS–/– mice. These observations suggest that neither eNOS nor nNOS is essential for up- or downregulation of renin expression. eNOS-derived NO appears to enhance renin expression, whereas nNOS-derived NO does not.