Role of endothelin－1 in experimental hypertensive rats

Role of endothelin-1 (ET-1) in the development and maintenance of hypertension is controversial. To search such a role of ET-1 , we investigated possible involvement of ET-1 in the pathogenesis of experimental hypertensive rats. In deoxycorticosterone (DOCA)-salt hypertensive rats, a significant increase in aortic immunoreactive-ET (IR-ET) level was observed compared with finding in agematched control rats. On the other hand, there were no significant changes in IR-ET levels in the kidney with DOCA-salt treatment. We found a significant correlation between aortic IR-ET levels and systolic blood pressure in DOCA-salt rats. The intravenous injection of FR139317 (10mg/kg). ET_A receptor antagonist, produced a slight decrease in blood pressure in control rats and FR139317 had a more pronounced hypotensive effect in the DOCA-salt hypertensive rats. FR139317 treatment to nitro-L-arginine-induced hypertensive rats and 2 kidney-1 clip (2KlC) renal hypertensive rats produce only a moderate hypotensive effect to the same degree as that in normotensive rats. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study suggests the pathophysiological importance of ET-1 and the ET_A receptor in DOCA-salt-induced hypertension but not in 2KlC renal hypertension and nitro-L-arginine-induced hypertension.