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pubmed:abstractText |
Intravenously administered endothelin-1 (ET-1) (2 x 10(-11)-6 x 10(-10) mol/kg) induced dose-dependent pressor responses in anesthetized guinea pigs. Pretreatment with indomethacin (5 mg/kg, i.v.) or with a thromboxane A2/prostaglandin endoperoxide receptor antagonist, ONO-3708 (0.5 and 1.0 mg/kg, i.v.) significantly attenuated the pressor responses. ET-1 (10(-11)-10(-7) M) dose-dependently contracted guinea pig pulmonary parenchymal strips in vitro. However, neither 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 with a platelet activating factor receptor antagonist, CV-3988 (2 x 10(-5) M) did not significantly affect the contraction. Thus, in guinea pigs, the mechanism of ET-1-induced pressor response in vivo mediated via cyclooxygenase-generated-eicosanoid(s), possibly, thromboxane A2 is not identical to that of ET-1-induced contraction of pulmonary parenchymal strips in vitro.
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