Incomplete inhibition of endothelin-1 pressor effects by an endothelin ETA receptor antagonist.
Incomplete inhibition of endothelin-1-induced pressor effects by FR-139317, a novel, potent, ETA receptor antagonist, was observed in conscious, normotensive rats. Maximum inhibition by FR-139317 of the endothelin-1 pressor response (0.1, 0.3, 1.0 nmol/kg) was 49 +/- 7, 41 +/- 3, 62 +/- 5%, respectively. Two ETB-selective receptor ligands induced pressor responses in conscious rats. A portion of the endothelin-1 pressor response may be mediated by ETB receptors, and ETB-mediated vasoconstriction may contribute to incomplete inhibition of the pressor response to endothelin-1 by an ETA-selective receptor antagonist.
Bird
J E
JE
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Waldron
T L
TL
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C079574:FR 139317