K. Fujita et al., ROLE OF ENDOTHELIN-1 AND THE ET(A) RECEPTOR IN THE MAINTENANCE OF DEOXYCORTICOSTERONE ACETATE-SALT-INDUCED HYPERTENSION, British Journal of Pharmacology, 114(5), 1995, pp. 925-930
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.