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

Our study aimed to assess the roles of nitric oxide derived from endotheliu m NO-synthase (eNOS) and macula densa neuronal NO-synthase (nNOS) in the re gulation 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 fee ding a low-salt (NaCl 0.02%) diet together with the converting-enzyme inhib itor ramipril (10 mg kg(-1) day(-1)). In all mouse strains, renin mRNA leve ls were inversely related to the rate of sodium intake. In eNOS-/- mice ren in mRNA levels and renal renin content were 50% lower than in wt mice at ea ch level of salt intake, whilst in nNOS-/- mice renin expression was not di fferent from wt controls. Administration of the general NO-synthase inhibit or nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1) day(-1)) to mice kep t on the low-salt/ramipril regimen caused a decrease of renal renin mRNA le vels in wt and nNOS-/- mice, but not in eNOS-/- mice. These observations su ggest that neither eNOS nor nNOS is essential for up- or downregulation of renin expression. eNOS-derived NO appears to enhance renin expression, wher eas nNOS-derived NO does not.