Phorbol Myristate Acetate Inhibits the Bradykinin-Induced L-Nitro-Arginine Insensitive Endothelium-Dependent Relaxation of Bovine Coronary Artery

The effects of L-nitro-arginine (LNAG) and phorbol myristate acetate (PMA) were studied in bradykinin-induced relaxations in bovine coronary arteries. In the presence of indomethacin (10 microM), neither LNAG (100 microM) nor PMA (0.1 microM) inhibited the bradykinin-induced relaxations in coronary arterial rings contracted with prostaglandin F2 alpha. However, simultaneous application of LNAG and PMA almost completely abolished the bradykinin-induced relaxation. In a sandwich-method, endothelium-intact coronary arteries (donor vessels) were treated with LNAG or with PMA for 30 min and then placed in close apposition to a denuded ring (assay vessel). Pretreatment of the donor vessels with LNAG, but not with PMA, almost completely abolished the bradykinin-induced relaxations in the assay vessel. In contrast, treatment of the assay vessel with PMA or with LNAG had no effect. These results suggest that bradykinin-induced endothelium-dependent relaxation of bovine coronary artery depends on both the release of nitric oxide and other endothelium-derived relaxing factor(s), which is an extremely labile substance(s), or a non-diffusible factor(s). PMA seems to inhibit the production and/or the release of the latter substance(s).