1. Inhibition of prostacyclin release from cultured endothelial cells by nitrovasodilator drugs.
- Author
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Matthews JS, McWilliams PJ, Key BJ, and Keen M
- Subjects
- Adenosine Triphosphate metabolism, Animals, Bradykinin pharmacology, Cattle, Cells, Cultured, Cyclic GMP analogs & derivatives, Cyclic GMP pharmacology, Drug Tolerance, Nitroglycerin pharmacology, Endothelium, Vascular drug effects, Epoprostenol metabolism, Nitroprusside pharmacology, Vasodilator Agents pharmacology
- 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.
- Published
- 1995
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