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

Pflugers Arch. 2000 Mar;439(5):567-72. doi: 10.1007/s004249900214.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure
  • DNA, Complementary
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gene Expression Regulation, Enzymologic / physiology
  • Hypertension, Renal / drug therapy
  • Hypertension, Renal / enzymology
  • Kidney / enzymology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • RNA, Messenger / analysis
  • Ramipril / pharmacology
  • Renin / genetics*
  • Sodium, Dietary / pharmacology
  • Water-Electrolyte Balance / genetics


  • Antihypertensive Agents
  • DNA, Complementary
  • Enzyme Inhibitors
  • RNA, Messenger
  • Sodium, Dietary
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos1 protein, mouse
  • Nos3 protein, mouse
  • Renin
  • Ramipril
  • NG-Nitroarginine Methyl Ester