Inhibition of prostacyclin release from cultured endothelial cells by nitrovasodilator drugs

• Published in: Biochimica et biophysica acta 1995-11, Vol.1269 (3), p.237-242
• Main Authors: Matthews, Jane S., McWilliams, Philip J., Key, Brian J., Keen, Mary
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Bradykinin - pharmacology; Cattle; Cells, Cultured; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Drug Tolerance; Endothelial cell; Endothelium, Vascular - drug effects; Epoprostenol - metabolism; Modulation; Nitric oxide; Nitroglycerin - pharmacology; Nitroprusside - pharmacology; Nitrovasodilator drug; Prostacyclin; Tolerance; Vasodilator Agents - pharmacology
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/0167-4889(95)00125-X

Pretreatment (18 h) of the bovine aortic endothelial cell line AG4762 to 500 μM sodium nitroprusside (SNP), glyceryl trinitrate (GTN) or 3-morpholino-sydronimine (SIN-1) significantly inhibited 100 nM bradykinin-stimulated prostacyclin (PGI 2) 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 PGI 2 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 PGI 2 release. We have demonstrated this inhibition of bradykinin-stimulated PGI 2 release is not the result of cell death. In addition, 8-bromo-cyclic GMP, whilst having no effect on basal PGI 2 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.