Role of endothelin-1 and the ETA receptor in the maintenance of deoxycorticosterone acetate-salt-induced hypertension.

1. To search for a possible role for endothelin-1 (ET-1) in deoxycorticosterone acetate (DOCA)-salt-induced hypertension, we examined changes in concentration of ET-1 in vascular and renal tissue in DOCA-salt hypertensive rats and evaluated the antihypertensive effect of the ETA receptor antagonist, FR139317. 2. There was an increase in aortic immunoreactive-ET (IR-ET) concentrations in association with hypertension-induced treatment. There were no significant changes in ET-1 levels in the kidney with DOCA-salt treatment. 3. In DOCA-salt hypertensive rats, a significant correlation (r = 0.83, P < 0.01) was found between aortic IR-ET concentrations and systolic blood pressure. 4. High-performance liquid chromatography analysis of the aortic extract from DOCA-salt rats revealed one major component corresponding to the elution position of synthetic ET-1. 5. The intravenous bolus injection of FR139317 (10 mg kg-1) produced a slight decrease in blood pressure in the control rats and in the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect. 6. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study indicates the pathophysiological importance of increased endogenous ET-1 in the maintenance of DOCA-salt-induced hypertension, through interaction of the peptide with ETA receptors.