Involvement of endothelin-1 in deoxycorticosterone acetate-salt-induced hypertension and cardiovascular hypertrophy.
The role of endothelin-1 (ET-1) in the development and maintenance of hypertension is controversial. To determine the role of ET-1, we investigated the possible involvement of ET-1 in the pathogenesis of experimental hypertensive rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a significant increase in aortic immunoreactive ET (IR-ET) level was observed, compared with age-matched sham-operated rats. Intravenous injection of the ETA receptor antagonist FR139317 (10 mg/kg) produced a slight decrease in blood pressure in sham rats. In the DOCA-salt hypertensive rats, FR139317 had a more pronounced hypotensive effect. Treatment with the antagonist in nitro-L-arginine (LNA)-induced hypertensive rats, two-kidney, one-clip (2K1C) renal hypertensive rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHR-SP) produced only moderate hypotensive effects, of the same degree as those in normotensive rats. Long-term treatment with FR139317 in DOCA-salt hypertensive rats efficiently suppressed the development of hypertension and cardiovascular hypertrophy. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study suggests the pathophysiologic importance of ET-1 and the ETA receptor in DOCA-salt-induced hypertension but not in SHR, in SHR-SP, in 2K1C renal hypertension, and in LNA-induced hypertension.
Matsumura
Y
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Fujita
K
K
Miyazaki
Y
Y
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000473:pathology*; D006332:Cardiomegaly / Q000209:etiology* / Q000517:prevention & control; D003900:Desoxycorticosterone; D016232:Endothelins / Q000502:physiology*; D006973:Hypertension / Q000209:etiology* / Q000517:prevention & control; D006984:Hypertrophy; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride
D001381:Azepines; D016232:Endothelins; D007211:Indoles; C079574:FR 139317; D003900:Desoxycorticosterone; D012965:Sodium Chloride