This Article Full Text (PDF) 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 Tokita, Y. Articles by Mulrow, P. J. Search for Related Content PubMed PubMed Citation Articles by Tokita, Y. Articles by Mulrow, P. J.

Hypertension, Vol 23, 422-427, Copyright © 1994 by American Heart Association

ARTICLES

Hypertension in the transgenic rat TGR(mRen-2)27 may be due to enhanced kinetics of the reaction between mouse renin and rat angiotensinogen

Y Tokita, R Franco-Saenz, EM Reimann and PJ Mulrow
Department of Medicine, Medical College of Ohio, Toledo.

The transgenic rat TGR(mRen-2)27, in which the Ren-2 mouse renin gene is transfected into the genome of the rat, develops severe hypertension with high adrenal renin and low kidney renin. These animals express both mouse and rat renin. To investigate the cause of hypertension in the TGR rat, we compared the kinetics of mouse renin acting on mouse and rat angiotensinogens. The optimum pH of the renin reaction in the Sprague-Dawley rat was 6.5, whereas the optimum pH of the reaction in the TGR rat was approximately 8.5. The optimum pH of the renin reaction in the DBA mouse was 6.0. Purified mouse Ren-2 renin acting on rat angiotensinogen showed a pH profile similar to that for the renin reaction in the TGR rat. The angiotensinogen concentration in pooled plasma from eight DBA mice was 104.5 ng angiotensin I/mL and was clearly lower than that in Sprague-Dawley rats (772.4 +/- 37.3 ng angiotensin I/mL, n = 4). The reaction of purified mouse Ren-2 renin with rat angiotensinogen was 10 times faster than with mouse angiotensinogen. Plasma renin activity in DBA mice increased dramatically on addition of rat angiotensinogen (from 253.4 +/- 66.7 to 225,000 +/- 48,000 ng angiotensin I/mL per hour). Intravenous injection of 2 or 10 microL of DBA mouse plasma into the nephrectomized Sprague- Dawley rat increased the mean arterial pressure of the rat by 27.7 +/- 4.7 and 61.8 +/- 2.7 mmHg, respectively, whereas injection of 200 microL of Sprague-Dawley rat plasma did not change the mean arterial pressure of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				T. L. Reudelhuber, K. E. Bernstein, and P. Delafontaine Is Angiotensin II a Direct Mediator of Left Ventricular Hypertrophy?: Time for Another Look Hypertension, June 1, 2007; 49(6): 1196 - 1201. [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]

				P. Rong, D. J. Campbell, and S. L. Skinner Hypertension in the (mRen-2)27 Rat Is Not Explained by Enhanced Kinetics of Transgenic Ren-2 Renin Hypertension, October 1, 2003; 42(4): 523 - 527. [Abstract] [Full Text] [PDF]

				J. Zhuo, M. Ohishi, and F. A. O. Mendelsohn Roles of AT1 and AT2 Receptors in the Hypertensive Ren-2 Gene Transgenic Rat Kidney Hypertension, January 1, 1999; 33(1): 347 - 353. [Abstract] [Full Text] [PDF]

				K. Tamura, S. Umemura, Y. Sumida, N. Nyui, S.-i. Kobayashi, T. Ishigami, M. Kihara, T. Sugaya, A. Fukamizu, H. Miyazaki, et al. Effect of Genetic Deficiency of Angiotensinogen on the Renin-Angiotensin System Hypertension, August 1, 1998; 32(2): 223 - 227. [Abstract] [Full Text] [PDF]

				J. Bohlender, J. Menard, O. Edling, D. Ganten, and F. C. Luft Mouse and rat plasma renin concentration and gene expression in (mRen2)27 transgenic rats Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1450 - H1456. [Abstract] [Full Text] [PDF]

				N. Makino, M. Sugano, S. Ohtsuka, and S. Sawada Intravenous Injection With Antisense Oligodeoxynucleotides Against Angiotensinogen Decreases Blood Pressure in Spontaneously Hypertensive Rats Hypertension, May 1, 1998; 31(5): 1166 - 1170. [Abstract] [Full Text] [PDF]

				M. Ehrhart-Bornstein, J. P. Hinson, S. R. Bornstein, W. A. Scherbaum, and G. P. Vinson Intraadrenal Interactions in the Regulation of Adrenocortical Steroidogenesis Endocr. Rev., April 1, 1998; 19(2): 101 - 143. [Abstract] [Full Text]

				C. Richer, P. Bruneval, J. Menard, and J.-F. Giudicelli Additive Effects of Enalapril and Losartan in (mREN-2)27 Transgenic Rats Hypertension, February 1, 1998; 31(2): 692 - 698. [Abstract] [Full Text] [PDF]

				N. Nyui, K. Tamura, S. Yamaguchi, M. Nakamaru, T. Ishigami, M. Yabana, M. Kihara, H. Ochiai, N. Miyazaki, S. Umemura, et al. Tissue Angiotensinogen Gene Expression Induced by Lipopolysaccharide in Hypertensive Rats Hypertension, October 1, 1997; 30(4): 859 - 867. [Abstract] [Full Text]

				M. Marttila, O. Vuolteenaho, D. Ganten, K. Nakao, and H. Ruskoaho Synthesis and Secretion of Natriuretic Peptides in the Hypertensive TGR(mREN-2)27 Transgenic Rat Hypertension, December 1, 1996; 28(6): 995 - 1004. [Abstract] [Full Text]

				M. W. Thompson, S. B. Smith, and C. D. Sigmund Regulation of Human Renin mRNA Expression and Protein Release in Transgenic Mice Hypertension, August 1, 1996; 28(2): 290 - 296. [Abstract] [Full Text]

				K. Tamura, S. Umemura, N. Nyui, T. Yamakawa, S. Yamaguchi, T. Ishigami, S.-i. Tanaka, K. Tanimoto, N. Takagi, H. Sekihara, et al. Tissue-Specific Regulation of Angiotensinogen Gene Expression in Spontaneously Hypertensive Rats Hypertension, June 1, 1996; 27(6): 1216 - 1223. [Abstract] [Full Text]

				M. Volpe, S. Rubattu, B. Gigante, D. Ganten, A. Porcellini, R. Russo, M. Romano, I. Enea, M. A. Lee, and B. Trimarco Regulation of Aldosterone Biosynthesis by Adrenal Renin Is Mediated Through AT1 Receptors in Renin Transgenic Rats Circ. Res., July 1, 1995; 77(1): 73 - 79. [Abstract] [Full Text]