Ameliorating effect of an endothelin ETA receptor antagonist on renal function of DOCA-salt hypertensive rats.
The effects of FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1 H-azepinyl)]-carbonyl]amino-4-methyl-pentanoyl]amino-3[3-(1-methyl -1 H-indolyl)]propionyl]amino-3-2(2-pyridyl)propionic acid), an endothelin ETA receptor antagonist, on renal hemodynamics and urine formation were examined using anesthetized deoxycorticosterone acetate (DOCA)-salt hypertensive rats, in which renal perfusion pressure was protected from FR139317-induced hypotension with an aortic clamp. An intravenous injection of FR139317 (10 mg/kg) to sham-operated normotensive control rats produced no significant changes in renal hemodynamic and excretory responses. In DOCA-salt hypertensive rats, FR139317 caused sustained renal vasodilation. Urine flow and urinary excretion of sodium were increased significantly following drug injection. We suggest that endothelin-1 and the endothelin ETA receptor play an important role in water and sodium retention, and in renal vasoconstriction in this model of hypertension.
Matsumura
Y
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Hashimoto
N
N
Fujita
K
K
Morimoto
S
S
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D007211:Indoles; D044022:Receptor, Endothelin A; C079574:FR 139317; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D012964:Sodium