Differential effect of cyclic GMP on the release of endothelin-1 from cultured endothelial cells and intact porcine aorta.
The effect of the inhibition of the release of endothelium-derived nitric oxide (NO) by L-NG-monomethylarginine (L-NMMA) on the production of endothelin-1 (ET-1) was studied both in intact porcine aorta and in cultured porcine aortic endothelial cells. The basal production of endothelin was not affected by L-NMMA or by SIN-1, but was significantly increased in the presence of thrombin under both experimental conditions. In the intact porcine aorta, the thrombin-stimulated release of the peptide was potentiated in the presence of L-NMMA, demonstrating that the thrombin-stimulated release of NO downregulates the concomitant production of endothelin. In contrast, in cultured endothelial cells obtained from the porcine aorta, L-NMMA did not affect the thrombin-stimulated release of the peptide, suggesting that the regulatory mechanism in cultured endothelial cells is not linked to the production of ET-1.
Boulanger
C M
CM
Department of Research, University Hospitals, Basel, Switzerland.
Lüscher
T F
TF
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000494:pharmacology*; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism; D011863:Radioimmunoassay; D013552:Swine; D013917:Thrombin / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016232:Endothelins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D013917:Thrombin; D006152:Cyclic GMP