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) (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.
Matsuda
H
H
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan.
Beppu
S
S
Ohmori
F
F
Miyatake
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D010742:Phospholipid Ethers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology
D016232:Endothelins; D010742:Phospholipid Ethers; D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; C037913:CV 3988; C049855:ONO 3708; D007213:Indomethacin