Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide.

Abstract

This study was designed to examine whether endothelin is re- leased from the intima of intact arteries, and whether endothe- lium-derived nitric oxide regulates its production.Endothelin was detected in the incubating medium of unstimulated pig aortae with, but not in those without endothelium.In prepara- tions with endothelium, thrombin (2-6 U/ml) and the calcium ionophore A23187 (10' M) stimulated the release of the pep- tide.The basal and thrombin-stimulated production of endo- thelin were prevented by the protein synthetase inhibitor cy- cloheximide (10-' M).The production of endothelin upon stimulation with thrombin (4 U/ml) was potentiated by L-NG- monomethyl arginine and methylene blue and reduced by su- peroxide dismutase and 8-bromo cyclic guanosine 5'-mono- phosphate (GMP), while the basal release of the peptide was unaffected.Thus, (a) endothelin is released from the intimal layer of intact blood vessels, both under basal conditions and after stimulation with thrombin and the calcium ionophore A23187, and (b) endothelium-derived nitric oxide released during stimulation with thrombin inhibits the production of the peptide via a cyclic GMP-dependent pathway.(J.Clin.Invest.1990.85:587-590.)calcium ionophore A23187 -cyclic guano- sine 5'-monophosphate * endothelium-derived relaxing factor-L-arginine pathway -thrombin 1. Abbreviations used in this paper: cGMP, cyclic guanosine 5'-mono- phosphate; L-NMMA, L-NG-monomethyl arginine.