Endothelium-derived relaxing factor inhibits platelet adhesion to cultured porcine endocardial endothelium.
By using a simple platelet binding assay, we investigated whether endothelium-derived relaxing factor (EDRF) released from endocardial endothelium influences the adhesion of unstimulated platelets to these cells. Under basal conditions 8.0 +/- 0.32% of total platelets added adhered. The nitric oxide (NO) synthase inhibitor, i.e. NG-nitro L-arginine methyl ester (L-NAME), and the EDRF inhibitor haemoglobin (Hb) increased this adhesion, but another NO synthase inhibitor, NG-monomethyl L-arginine (L-NMMA), did not. The EDRF releasing agent substance P (SP) decreased adhesion, L-NMMA reversed this inhibition, whereas L-NAME and Hb did so only partially. Superoxide dismutase (SOD) caused a marked decrease in adhesion which was fully reversed by L-NMMA, L-NAME and Hb. SOD and SP together showed a cumulative effect on platelet adhesion; this inhibition was significantly reversed by all the EDRF inhibitors, although the levels of adhesion did not return to those seen under basal conditions. These results indicate that EDRF release can inhibit the adhesion of unstimulated platelets to cultured porcine endocardium and that NO synthase inhibitors have differential effects on basal and stimulated EDRF release by these cells.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004699:Endocardium / Q000166:cytology / Q000502:physiology*; D004727:Endothelium / Q000166:cytology / Q000502:physiology*; D006454:Hemoglobins / Q000494:pharmacology; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine; D019323:omega-N-Methylarginine
D006454:Hemoglobins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester