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(Hypertension. 1998;32:746-752.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Effects of Eprosartan on Renal Function and Cardiac Hypertrophy in Rats With Experimental Heart Failure

Sergey Brodsky; Konstantin Gurbanov; Zaid Abassi; Aaron Hoffman; Robert R. Ruffolo, Jr; Giora Z. Feuerstein; ; Joseph Winaver

From the Department of Physiology and Biophysics, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (S.B., K.G., Z.A., A.H., J.W.), and Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa (R.R.R., G.Z.F.).

Correspondence to Joseph Winaver, MD, Department of Physiology and Biophysics, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St 1, POB 9649, Haifa 31096, Israel. E-mail winaver{at}tx.technion.ac.il

Abstract—Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with aortocaval fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with aortocaval fistula produced a significant increase (+34%) in total renal blood flow and a sustained decrease (-33%) in the calculated renal vascular resistance. These effects on renal hemodynamics were more pronounced than those observed in sham-operated control rats and occurred despite a significant fall (-12%) in mean arterial blood pressure. Moreover, eprosartan caused a preferential increase in renal cortical blood perfusion and significantly increased glomerular filtration in rats with congestive heart failure. Chronic administration of eprosartan (5.0 mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on the day of operation) resulted in a significant enhancement of urinary sodium excretion compared with nontreated rats with heart failure. Moreover, administration of eprosartan to salt-retaining rats with congestive heart failure resulted in a progressive increase and ultimate recovery in urinary sodium excretion. Finally, early treatment with eprosartan blocked the development of cardiac hypertrophy in rats with aortocaval fistula to a larger extent than the angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the importance of angiotensin II in mediating the impairment in renal function and induction of cardiac hypertrophy in heart failure and further suggest that angiotensin II receptor blockade may be a useful treatment of these consequences in severe cardiac failure.

Key Words: angiotensin II • angiotensin antagonist • fistula, aortocaval • hypertrophy • renal circulation • hemodynamics • rats

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