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.