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 ET A 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 ET A receptor in DOCA-salt-induced hypertension but not in SHR, in SHR-SP, in 2K1C renal hypertension, and in LNA-induced hypertension.