NITRIC-OXIDE SYNTHASE IN CULTURED ENDOCARDIAL CELLS OF THE PIG

1 Endocardial cells release factors which regulate myocardial contractility and guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels. One of these factors is indistinguishable from endothelium-derived relaxing factor (EDRF). 2 The effluent from pig heart endocardial cells cultured on microcarrier beads caused the relaxation of a pig coronary artery ring denuded of endothelium. This relaxation was enhanced by a combination of superoxide dismutase and catalase and was attenuated by haemoglobin, which binds nitric oxide (NO), and by inhibitors of NO synthase, N(G)-monomethyl-L-arginine (L-NMMA) or N(G)-nitro-L-arginine. 3 A Ca2+-, L-arginine- and NADPH-dependent enzyme activity which generated NO was detected by a specific spectrophotometric assay in cytosol prepared from endocardial cells. The formation of NO was inhibited in a concentration-dependent manner by L-NMMA (but not D-NMMA) and this could be partially reversed upon addition of excess L-arginine. 4 Like endothelial cells from the blood vessels, the endocardial cells possess the ability to synthesize NO, which may act to regulate myocardial contractility.