DIFFERENT MODES OF ENDOTHELIN-1 ACTION IN PRESSOR-RESPONSE IN-VIVO AND PULMONARY PARENCHYMAL CONTRACTION IN-VITRO IN THE GUINEA-PIG

Intravenously administered endothelin-1 (ET-1) (2x10(-11) similar to 6 x10(-10) mol/kg) induced dose-dependent pressor responses in anestheti zed guinea pigs. Pretreatment with indomethacin (5 mg/kg, i.v.) or wit h a thromboxane A(2)/prostaglandin endoperoxide receptor antagonist, O NO-3708 (0.5 and 1.0 mg/kg, i.v.) significantly attenuated the pressor responses. ET-1 (10(-11) similar to 10(-7) M) dose-dependently contra cted guinea pig pulmonary parenchymal strips in vitro. However, neithe r pretreatment with indomethacin (10(-5) M) nor one with ONO-3708 (10( -6) M and 10(-5) M) significantly affected the ET-1-induced guinea pig pulmonary parenchymal contraction in vitro. Moreover, pretreatment wi th a platelet activating factor receptor antagonist, CV-3988 (2x10(-5) M) did not significantly affect the contraction. Thus, in guinea pigs , the mechanism of ET-1-induced pressor response in vivo mediated via cyclo-oxygenase-generated-eicosanoid(s), possibly, thromboxane A(2) is not identical to that of ET-1-induced contraction of pulmonary parenc hymal strips in vitro.