title: Inhibition of prostacyclin release from cultured endothelial cells by nitrovasodilator drugs.
abstract: Pretreatment (18 h) of the bovine aortic endothelial cell line AG4762 to 500 microM sodium nitroprusside (SNP), glyceryl trinitrate (GTN) or 3-morpholino-sydnonimine (SIN-1) significantly inhibited 100 nM bradykinin-stimulated prostacyclin (PGI2) release. SIN-1 produced the greatest reduction (67 +/- 6%), followed by SNP (47 +/- 12%) and GTN (45 +/- 9%). Only SIN-1 and GTN inhibited basal PGI2 release where again the effect of SIN-1 (66 +/- 6%) was greater than that of GTN (31 +/- 15%). There was no effect of SNP on basal PGI2 release. We have demonstrated this inhibition of bradykinin-stimulated PGI2 release is not the result of cell death. In addition, 8-bromo-cyclic GMP, whilst having no effect on basal PGI2 release, demonstrated a small but significant inhibition (15 +/- 6%) of the enhanced response to 100 nM bradykinin. These studies may reflect a mechanism by which the release of vasodilators from endothelial cells is altered during therapy with nitrovasodilators and thus may contribute to the development of tolerance to these drugs.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000187:drug effects*; D011464:Epoprostenol / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D005996:Nitroglycerin; D006152:Cyclic GMP; D001920:Bradykinin