Comparative effects of nitroglycerin and nitroprusside on prostacyclin generation in adult human vessel wall.
The precise mechanism of vasodilatory actions of nitroso-compounds is not clear. It has been suggested that these drugs might modulate release of the vasodilator, prostacyclin, from cultured endothelial cells and bovine arteries or potentiate actions of prostacyclin. This study was designed to examine the effects of nitroglycerin and nitroprusside on prostacyclin release from adult human vasculature. Saphenous vein ring preparations were incubated with nitroglycerin or nitroprusside and arachidonic acid, the substrate for prostacyclin. Vascular rings incubated with nitroglycerin released significantly more prostacyclin (measured as 6-keto-prostaglandin F1 alpha, a stable hydrolysis product of prostacyclin by radioimmunoassay) compared with the control vascular rings (p less than 0.02). This increase was observed at the therapeutic concentrations of nitroglycerin (5 to 10 ng/ml). However, incubation of saphenous vein rings with nitroprusside in concentrations as high as 1 microgram/ml was not associated with any increase in prostacyclin release. Prior incubation of vascular rings with the cyclooxygenase blocker, indomethacin, inhibited nitroglycerin-induced prostacyclin release. Incubation of vascular rings with the selective thromboxane A2 blocker, OKY 1581, resulted in additional prostacyclin release with nitroglycerin treatment, presumably by inhibiting vessel wall-generated thromboxane A2. Nitroprusside had no significant effect on prostacyclin release from indomethacin-treated or OKY 1581-treated vascular rings. This study suggests significant stimulatory effects of nitroglycerin, but not of nitroprusside, on prostacyclin release from human saphenous vein. Nitroglycerin-induced prostacyclin release may be an important mechanism of its antiischemic actions in human subjects.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis*; D005292:Ferricyanides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D005292:Ferricyanides; D008689:Methacrylates; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D009599:Nitroprusside; D015121:6-Ketoprostaglandin F1 alpha; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D005996:Nitroglycerin; D007213:Indomethacin