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 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.
Wagner
C
C
Institut für Physiologie I, Universität Regensburg, Germany.
Gödecke
A
A
Ford
M
M
Schnermann
J
J
Schrader
J
J
Kurtz
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D018076:DNA, Complementary; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000201:enzymology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000032:analysis; D017257:Ramipril / Q000494:pharmacology; D012083:Renin / Q000235:genetics*; D012982:Sodium, Dietary / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000235:genetics
D000959:Antihypertensive Agents; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012982:Sodium, Dietary; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D012083:Renin; D017257:Ramipril; D019331:NG-Nitroarginine Methyl Ester