Actions of nitric oxide on the release of prostacyclin from bovine endothelial cells in culture.
Endothelial cells release the potent vasodilator prostacyclin, as well as the highly labile endothelium-derived relaxing factor (EDRF) which mediates vascular relaxation induced by some vasodilators including acetylcholine and bradykinin. EDRF has recently been characterised as nitric oxide (NO). The effects of NO on prostacyclin release, measured as 6-keto-PGF1 alpha, from endothelial cells obtained from bovine thoracic aorta, have now been investigated. Incubation of endothelial cells in culture with bradykinin (10-100 nM) stimulated the release of 6-keto-PGF1 alpha. Pre-incubation (0.5-2 min) with NO (13-130 microM) caused a significant dose-dependent inhibition of 6-keto-PGF1 alpha release, reaching a maximum of 29 +/- 4% inhibition. Pre-incubation with superoxide dismutase (30 units ml-1) which prevents the breakdown of NO, significantly augmented the degree of inhibition, as did the selective inhibitor of cyclic GMP phosphodiesterase, M & B 22948 (5 microM), reaching 51 +/- 2% inhibition. The potentiation by M & B 22948 suggests that this inhibitory effect of high concentrations of NO is brought about by elevation of intracellular cyclic GMP levels following activation of guanylate cyclase. Whether endogenous NO is produced by endothelial cells under physiological conditions in sufficient quantities to modulate prostacyclin release remains to be established.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001688:Biological Products / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology; D011863:Radioimmunoassay; D013482:Superoxide Dismutase / Q000494:pharmacology
D001688:Biological Products; D011688:Purinones; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D013482:Superoxide Dismutase; C011145:zaprinast; D001920:Bradykinin