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 (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.
Tanabe
A
A
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan. RXK00525@niftyserve.or.jp
Naruse
M
M
Adachi
C
C
Seki
T
T
Yoshimoto
T
T
Takagi
S
S
Naruse
K
K
Takano
K
K
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology*; D019332:Endothelin-1 / Q000235:genetics*; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D019332:Endothelin-1; D012333:RNA, Messenger; D006830:Hydralazine