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(Hypertension. 2004;43:79.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Cardiovascular and Renal Phenotype in Mice With One or Two Renin Genes

From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit Medical Campus of Case Western Reserve University School of Medicine, Detroit, Mich.

Correspondence to William H. Beierwaltes, PhD, Professor of Medicine, Senior Staff Scientist Hypertension and Vascular Research Division, Henry Ford Hospital and Health Sciences Center, 2799 W Grand Blvd, Detroit, MI. E-mail wbeierw1{at}hfhs.org

We compared the phenotype of two common mouse models, C-57BL/6J (C57), which carries only the Ren-1^c gene, and 129/SvJ (Sv-129), with both Ren 1^d and Ren-2. We hypothesized two renin gene Sv-129 would have increased blood pressure and the renin-angiotensin system would be more influential in regulating renal function compared with one renin gene mice. Sv-129 consistently had higher blood pressure than C-57, whether conscious (128 versus 108 mm Hg, P<0.001) or anesthetized (102 versus 88 mm Hg, P<0.001). Plasma renin concentration in both conscious and anesthetized C-57 mice was 3- to 4-fold higher than in Sv-129 (P<0.05), whereas renal cortical renin content was 2.5-fold higher (P<0.005). Renal blood flow and renal vascular resistance were the same in C-57 and Sv-129. Exogenous angiotensinogen produced identical pressor and renal vasoconstrictor responses in both strains. Blocking AT₁ receptors with losartan reduced blood pressure by 19 mm Hg in both strains. Nitric oxide synthase inhibition by L-NAME increased blood pressure by 29 mm Hg in C-57 and 35 mm Hg in Sv-129 mice, but the decrease in renal blood flow was 30% less in C-57 (P<0.025). We conclude that Sv-129 mice with two renin genes have higher blood pressure but lower plasma and renal renin than C-57 mice with one renin gene. Renin substrate may limit angiotensin II production in the mouse. In Sv-129, the influence of nitric oxide on renal but not systemic resistance may be exaggerated. Renin from Ren-2 may act independently of normal renin control mechanisms.

Key Words: angiotensin • angiotensinogen • endothelium • mouse • nitric oxide • nitric oxide synthase • renin

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