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(Hypertension. 2006;47:552.)
© 2006 American Heart Association, Inc.

Part 2 Original Articles

Elevated Blood Pressure and Heart Rate in Human Renin Receptor Transgenic Rats

Céline A. Burcklé; A.H. Jan Danser; Dominik N. Müller; Ingrid M. Garrelds; Jean-Marie Gasc; Elena Popova; Ralph Plehm; Jörg Peters; Michael Bader; Geneviève Nguyen

From the Inserm U36 (C.A.B., G.N., J.M.G.), Paris, France; Collège de France (C.A.B., G.N., J.M.G.), Experimental Medicine Unit, Paris, France; Max Delbrück Center for Molecular Medicine (M.B., C.A.B., E.P., R.P.) and Franz Volhard Clinic (D.N.M.), Berlin, Germany; Institute for Physiology (J.P.), University Greifswald, Greifswald, Germany; and Department of Pharmacology (A.H.J.D., I.M.G.), Erasmus MC, Rotterdam, the Netherlands.

Correspondence to Michael Bader, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle Strasse 10, 13125 Berlin-Buch, Germany, E-mail mbader{at}mdc-berlin.de

Recently, a receptor for renin was described that may be important for vascular uptake and activation of (pro)renin, thus leading to local generation of angiotensin II. To assess the in vivo relevance of this protein, we generated transgenic rats overexpressing the human renin receptor gene in smooth muscle tissue, under the control of a 16-kb fragment of the mouse smooth muscle myosin heavy chain gene [TGR(SMMHC-HRR)]. Four lines of transgenic animals were obtained. The correct pattern of expression of the transgene was confirmed by RNase protection assay and in situ hybridization. TGR(SMMHC-HRR) rats are fertile and develop normally. After 6 months of age, transgenic rats develop a cardiovascular phenotype with an elevated systolic blood pressure (137.8±5 versus 118.9±3.7 mm Hg; P=0.008), and an augmentation in heart rate (349.1±7.7 versus 303.1±16.16 bpm; P=0.023) in TGR(SMMHC-HRR) and controls, respectively. These alterations are progressively increasing with aging. Although kidney function and plasma renin were normal in TGR(SMMHC-HRR), an increase in plasma aldosterone [TGR(SMMHC-HRR) 428±64.9 versus 207.3±73.24 pg/mL in control; P=0.02] and in aldosterone/renin ratio [TGR(SMMHC-HRR) 8.04±2.2 versus 2.8±0.55 in control; P=0.03] was observed. This suggests that renin receptor overexpression has resulted in increased intraadrenal angiotensin II, thereby provoking enhanced aldosterone generation in the absence of changes in plasma renin. The rise in aldosterone may underlie, at least in part, the observed cardiovascular phenotype of TGR(SMMHC-HRR).

Key Words: renin • rats, transgenic • blood pressure

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