INCOMPLETE INHIBITION OF ENDOTHELIN-1 PRESSOR EFFECTS BY AN ENDOTHELIN ET(A)-RECEPTOR ANTAGONIST

Incomplete inhibition of endothelin-1-induced pressor effects by FR-13 9317, a novel, potent, ET(A) receptor antagonist, was observed in cons cious, normotensive rats. Maximum inhibition by FR-139317 of the endot helin-1 pressor response (0.1, 0.3, 1.0 nmol/kg) was 49 +/- 7, 41 +/- 3, 62 +/- 5%, respectively. Two ET(B)-selective receptor ligands induc ed pressor responses in conscious rats. A portion of the endothelin-I pressor response may be mediated by ET(B) receptors, and ET(B)-mediate d vasoconstriction may contribute to incomplete inhibition of the pres sor response to endothelin-1 by an ET(A)-selective receptor antagonist .