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-N(G)-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.