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.
Fujita
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Kita
S
S
Miyazaki
Y
Y
Hisaki
K
K
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D017466:Receptors, Endothelin; C079574:FR 139317; D003900:Desoxycorticosterone