Hydralazine decreases blood pressure and endothelin-1 mRNA expression in tissues but not cardiac weight in SHR-SP/Izm rats

Although evidence has been accumulated to support a role of endothelin-1 (E T-1) in cardiac hypertrophy, details of the pathophysiological significance of ET-1 in cardiac hypertrophy remain to be elucidated. In the present stu dy, 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 th e kidney, heart, aorta and brain were obtained at the age of 12 weeks. Tiss ue expression of ET-1 mRNA was determined by reverse transcriptase polymera se chain reaction (RT-PCR) followed by Southern blot analysis. Administrati on of hydralazine resulted in a significant decrease in the blood pressure (156 +/- 1 mmHg vs 212 +/- 3 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 m g/100 g body weight vs 307 +/- 5 mg/100 g body weight in controls). The dis sociation between ET-1 mRNA expression and cardiac hypertrophy in hydralazi ne-treated rats may suggest that the increased tissue ET-1 is not an indisp ensable factor of cardiac hypertrophy in hypertension. Sympathetic activati on, as shown by the reactive tachycardia, may overcome the effects on the b lood pressure and ET-1 expression.