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(Hypertension. 2004;43:1233.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Prevention of Cardiac Hypertrophy by Angiotensin II Type-2 Receptor Gene Transfer

Beverly L. Metcalfe; Matthew J. Huentelman; Leonard D. Parilak; David G. Taylor; Michael J. Katovich; Harm J. Knot; Colin Sumners; Mohan K. Raizada

From the Departments of Physiology and Functional Genomics (B.L.M., M.J.H., M.K.R.), Pharmacology (D.G.T., H.J.K.), and Cardiovascular Medicine (L.D.P.), College of Medicine and the Evelyn F. and William L. McKnight Brain Institute; and the Department of Pharmacodynamics (M.J.K.), College of Pharmacy, University of Florida, Gainesville.

Correspondence to Mohan K. Raizada, Department of Physiology and Functional Genomics, University of Florida, College of Medicine, PO Box 100274, Gainesville, FL 32610. E-mail mraizada{at}phys.med.ufl.edu

The role of the angiotensin II type-2 receptor (AT₂R) in cardiac hypertrophy remains elusive despite its demonstrated involvement in cardiovascular development. We have previously shown that a lentiviral vector gene delivery system is able to transduce cardiac tissue with high efficiency in vivo. Using such an approach, our objectives in the present study were 2-fold: (1) to overexpress the AT₂R in cardiac tissue after completion of natural embryonic development of the heart and (2) to determine the effects of this overexpression on cardiac hypertrophy and basal blood pressure (BP). A lentiviral vector encoding the AT₂R (lenti-AT₂R) was administered (1.5x10⁸ transducing units) into the left ventricular space of 5-day-old spontaneously hypertensive rats (SHRs). AT₂R transgene expression increased in these animals and persisted for 30 weeks. In contrast, the expression of the angiotensin II type-1 receptor remained unchanged following lenti-AT₂R treatment. At 21 weeks following gene transduction, the lenti-AT₂R–treated SHRs exhibited decreased left ventricular wall thickness compared with control animals. In contrast, basal BP did not differ between the two SHR groups. Finally, heart weight to body weight ratios indicated a significant decrease in lenti-AT₂R-treated SHRs compared with SHR controls. Our data indicate that AT₂R overexpression attenuates cardiac hypertrophy in the SHR. This beneficial outcome was observed despite the existence of elevated BP.

Key Words: genes • receptors, angiotensin II • hypertrophy

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