Differential Effect of Cyclic GMP on the Release of Endothelin-1 from Cultured Endothelial Cells and Intact Porcine Aorta

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Abstract
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.

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