Endothelin ET(B) receptor-mediated action on systemic and renal hemodynamics and urine formation in deoxycorticosterone acetate-salt-induced hypertensive rats.
The pathophysiological role of endothelin ET(B) receptor-mediated action on systemic and renal hemodynamics and urine formation in deoxYcorticosterone acetate (DOCA)-salt hypertensive rats was investigated. An intravenous bolus injection of a selective ET(B) receptor antagonist, BQ788 (1 mg/kg), produced a significant increase in mean arterial pressure (MAP) of DOCA-salt treated rats, whereas the agent-induced increase in MAP was less marked in normotensive sham rats. Administration of BQ788 caused a significant and sustained reduction in renal blood flow both in DOCA-salt and sham rats. No marked effects were observed on urine formation in both groups. Alternatively, a selective ET(A) receptor antagonist, FR139317 (10 mg/kg), produced a potent hypotensive effect, accompanied by significant renal vasodilation in DOCA-salt hypertensive rats, but these effects were partially reversed by the subsequent administration of BQ788. When renal perfusion pressure was protected from FR139317-induced hypotension by an aortic clamp, significant diuresis and natriuresis were observed, events partially reversed by the subsequent administration of BQ788. Our results indicate that the ET(B) receptor-mediated action tonically functions as a hypotensive and a renal vasodilatory factor and that these effects seem to be up-regulated in DOCA-salt hypertension. We also suggest that the ET(A) receptor blockade in DOCA-salt hypertensive rats unmasks the ET(B) receptor-mediated action which partially contributes to the antihypertensive effect induced by FR139317.
Hashimoto
N
N
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Kuro
T
T
Fujita
K
K
Azuma
S
S
Matsumura
Y
Y
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D014554:Urination / Q000187:drug effects*
D001381:Azepines; D019332:Endothelin-1; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C079574:FR 139317; D003900:Desoxycorticosterone; C086539:BQ 788