ROLE OF ENDOTHELIN-1 AND THE ET(A) RECEPTOR IN THE MAINTENANCE OF DEOXYCORTICOSTERONE ACETATE-SALT-INDUCED HYPERTENSION

1 To search for a possible role for endothelin-1 (ET-1) in deoxycortic osterone acetate (DOCA)-salt-induced hypertension, we examined changes in concentration of ET-I in vascular and renal tissue in DOCA-salt hy pertensive rats and evaluated the antihypertensive effect of the ET(A) receptor antagonist, FR139317. 2 There was an increase in aortic immu noreactive-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 l iquid chromatography analysis of the aortic extract from DOCA-salt rat s revealed one major component corresponding to the elution position o f synthetic ET-1. 5 The intravenous bolus injection of FR139317 (10 mg kg(-1)) produced a slight decrease in blood pressure in the control r ats and in the DOCA-salt hypertensive rat, FR139317 had a more pronoun ced hypotensive effect. 6 We propose that ET-I production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study indicates the pathophysiological importance of increased endogen ous ET-1 in the maintenance of DOCA-salt-induced hypertension, through interaction of the peptide with ET(A) receptors.