Although evidence has been accumulated to support a role of endothelin-1 (ET-1) in cardiac hypertrophy, details of the pathophysiological significance of ET-1 in cardiac hypertrophy remain to be elucidated. In the present study, we investigated the effects of the vasodilator hydralazine on the blood pressure, cardiac hypertrophy and ET-1 gene expression in various tissues of spontaneously hypertensive rats (SHR-SP/Izm). Hydralazine (20 mg/kg/day) was administered orally from the age of 4 weeks for 8 weeks. Tissues of the kidney, heart, aorta and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Administration of hydralazine resulted in a significant decrease in the blood pressure (156 ± 1 mmHg vs 212 ± 4 mmHg in controls) and an increase in the heart rate (470 ± 20 bpm vs 402 ± 23 bpm in controls). ET-1 mRNA expression was significantly decreased in the heart (x 1/2), kidney (x 1/4) and brain (x 1/2). There was no significant change of the cardiac weight (309 ± 4 mg/100 g body weight vs 307 ± 5 mg/100 g body weight in controls). The dissociation between ET-1 mRNA expression and cardiac hypertrophy in hydralazine-treated rats may suggest that the increased tissue ET-1 is not an indispensable factor of cardiac hypertrophy in hypertension. Sympathetic activation, as shown by the reactive tachycardia, may overcome the effects on the blood pressure and ET-1 expression.
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Tokyo, Japan
Address correspondence and reprint requests to Akiyo Tanabe, Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail: [email protected]
© 2000 Lippincott Williams & Wilkins, Inc.