H. Matsuda et al., DIFFERENT MODES OF ENDOTHELIN-1 ACTION IN PRESSOR-RESPONSE IN-VIVO AND PULMONARY PARENCHYMAL CONTRACTION IN-VITRO IN THE GUINEA-PIG, Prostaglandins, 46(6), 1993, pp. 479-492
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.