Bradykinin produces pulmonary vasodilation in fetal lambs: role of prostaglandin production.
Bradykinin produces pulmonary vasodilation and also stimulates production of other pulmonary vasodilators, including prostaglandin I2 (PGI2) and endothelial-derived relaxing factor. In 12 chronically instrumented fetal lambs, we therefore investigated potential mediation of the bradykinin response by PGI2 or other cyclooxygenase products. A 15-min infusion of bradykinin (approximately 1 microgram/kg estimated fetal wt/min) increased fetal pulmonary blood flow by 522% (P less than 0.05) and decreased pulmonary vascular resistance by 86% (P less than 0.05); plasma 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentration also increased (P less than 0.05). After cyclooxygenase inhibition by indomethacin (3 mg), bradykinin increased pulmonary blood flow by only 350% (P less than 0.05) and decreased pulmonary vascular resistance by 83% (P less than 0.05); plasma 6-keto-PGF1 alpha concentrations did not increase. The increase in pulmonary blood flow produced by bradykinin was greater before administration of indomethacin than after (P less than 0.05). These studies demonstrate that bradykinin produces fetal pulmonary vasodilation by at least two mechanisms, one dependent on and the other independent of PGI2 production, the latter mechanism predominating.
Frantz
E
E
Cardiovascular Research Institute, University of California, San Francisco 94143.
Soifer
S J
SJ
Clyman
R I
RI
Heymann
M A
MA
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000196:embryology*; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D001920:Bradykinin; D007213:Indomethacin