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(Hypertension. 2002;40:251.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Perindopril Effect on Uncoupling Protein and Energy Metabolism in Failing Rat Hearts

Kazushi Murakami; Katsufumi Mizushige; Takahisa Noma; Teppei Tsuji; Shoji Kimura; Masakazu Kohno

From the Second Department of Internal Medicine (K. Murakami, K. Mizushige, T.N., T.T., M.K.) and Department of Pharmacology (S.K.), Kagawa Medical University, Kagawa, Japan.

Correspondence to Katsufumi Mizushige, MD, PhD, Second Department of Internal Medicine, Kagawa Medical University, 1750-1, Miki, Kita, Kagawa 761-0793 Japan. E-mail katsumz{at}kms.ac.jp

Uncoupling proteins, inner mitochondrial membrane proton transporters, are important for regulating myocardial energy efficiency. We investigated the effects of the ACE inhibitor perindopril on cardiac performance, myocardial energy efficiency, and uncoupling protein expression in an aortic regurgitation rat model. Twenty male Sprague-Dawley rats, in which aortic regurgitation was produced, were divided into untreated and perindopril-treated (5 mg · kg^-1 · d^-1) rats. The treatments were initiated 3 days after operation. Ten control rats were sham-operated. Measurements of blood pressure and echocardiography were repeated before and 100 days after operation (endpoint). Left ventricular uncoupling protein-2 expression, creatine phosphate, and adenosine triphosphate were measured at endpoint. In perindopril-treated rats, systolic and diastolic blood pressure decreased after treatment (92±4/65±2 mm Hg). At endpoint, left ventricular end-diastolic dimension in untreated (10.7±0.2 mm) and treated rats (9.2±0.2 mm) was increased, and fractional shortening was reduced in untreated rats (28±1%) but did not change in treated rats (36±2%). Uncoupling protein-2 mRNA expression increased in untreated rats (3.7-fold) and was suppressed by perindopril (1.5-fold). The creatine phosphate was reduced in untreated rats (10.6±0.7 µmol/g) but not in treated rats (15.9±2.0 µmol/g). In the chronic stage of aortic regurgitation, perindopril improved cardiac performance and myocardial energy efficiency, in which the suppression of uncoupling protein-2 may play an important role.

Key Words: uncoupling proteins • heart failure • metabolism • angiotensin-converting enzyme • rats • cardiac function

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