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, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine. 3. A Ca(2+)-, 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.
Schulz
R
R
Wellcome Research Laboratories, Beckenham, Kent.
Smith
J A
JA
Lewis
M J
MJ
Moncada
S
S
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D004699:Endocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D013552:Swine; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002118:Calcium