This Article Full Text Full Text (PDF) All Versions of this Article: 43/1/79    most recent 01.HYP.0000107401.72456.50v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lum, C. Articles by Beierwaltes, W. H. Search for Related Content PubMed PubMed Citation Articles by Lum, C. Articles by Beierwaltes, W. H.

(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

This article has been cited by other articles:

				Y. H. Kim, V. Pech, K. B. Spencer, W. H. Beierwaltes, L. A. Everett, E. D. Green, W. Shin, J. W. Verlander, R. L. Sutliff, and S. M. Wall Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1314 - F1324. [Abstract] [Full Text] [PDF]

				E. D. van Deel, D. Merkus, R. van Haperen, M. C. de Waard, R. de Crom, and D. J. Duncker Vasomotor control in mice overexpressing human endothelial nitric oxide synthase Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1144 - H1153. [Abstract] [Full Text] [PDF]

				N. Moore, P. Dicker, J. K. O'Brien, M. Stojanovic, R. M. Conroy, A. Treumann, E. T. O'Brien, D. Fitzgerald, D. Shields, and A. V. Stanton Renin Gene Polymorphisms and Haplotypes, Blood Pressure, and Responses to Renin-Angiotensin System Inhibition Hypertension, August 1, 2007; 50(2): 340 - 347. [Abstract] [Full Text] [PDF]

				H. Lu, C. M. Boustany-Kari, A. Daugherty, and L. A. Cassis Angiotensin II increases adipose angiotensinogen expression Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1280 - E1287. [Abstract] [Full Text] [PDF]

				C. J. Barrick, M. Rojas, R. Schoonhoven, S. S. Smyth, and D. W. Threadgill Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal- and background-dependent development of concentric left ventricular hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2119 - H2130. [Abstract] [Full Text] [PDF]

				N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]

				M. C. Ortiz-Capisano, P. A. Ortiz, P. Harding, J. L. Garvin, and W. H. Beierwaltes Adenylyl Cyclase Isoform V Mediates Renin Release From Juxtaglomerular Cells Hypertension, March 1, 2007; 49(3): 618 - 624. [Abstract] [Full Text] [PDF]

				M. C. Ortiz-Capisano, P. A. Ortiz, P. Harding, J. L. Garvin, and W. H. Beierwaltes Decreased Intracellular Calcium Stimulates Renin Release via Calcium-Inhibitable Adenylyl Cyclase Hypertension, January 1, 2007; 49(1): 162 - 169. [Abstract] [Full Text] [PDF]

				J. W. Verlander, Y. H. Kim, W. Shin, T. D. Pham, K. A. Hassell, W. H. Beierwaltes, E. D. Green, L. Everett, S. W. Matthews, and S. M. Wall Dietary Cl- restriction upregulates pendrin expression within the apical plasma membrane of type B intercalated cells Am J Physiol Renal Physiol, October 1, 2006; 291(4): F833 - F839. [Abstract] [Full Text] [PDF]

				R. D. Brown, P. Thoren, A. Steege, R. Mrowka, J. Sallstrom, O. Skott, B. B. Fredholm, and A. E. G. Persson Influence of the adenosine A1 receptor on blood pressure regulation and renin release Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1324 - R1329. [Abstract] [Full Text] [PDF]

				L. J. Mullins, M. A. Bailey, and J. J. Mullins Hypertension, Kidney, and Transgenics: A Fresh Perspective Physiol Rev, April 1, 2006; 86(2): 709 - 746. [Abstract] [Full Text] [PDF]

				S. M. Wall, M. A. Knepper, K. A. Hassell, M. P. Fischer, A. Shodeinde, W. Shin, T. D. Pham, J. W. Meyer, J. N. Lorenz, W. H. Beierwaltes, et al. Hypotension in NKCC1 null mice: role of the kidneys Am J Physiol Renal Physiol, February 1, 2006; 290(2): F409 - F416. [Abstract] [Full Text] [PDF]

				T. Yang, Y. G. Huang, W. Ye, P. Hansen, J. B. Schnermann, and J. P. Briggs Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1125 - F1132. [Abstract] [Full Text] [PDF]

				A. Daugherty, D. L. Rateri, H. Lu, T. Inagami, and L. A. Cassis Hypercholesterolemia Stimulates Angiotensin Peptide Synthesis and Contributes to Atherosclerosis Through the AT1A Receptor Circulation, December 21, 2004; 110(25): 3849 - 3857. [Abstract] [Full Text] [PDF]