ENHANCEMENT OF THE VASOCONSTRICTOR RESPONSE TO KCL BY NITRIC-OXIDE SYNTHESIS INHIBITION - A COMPARISON WITH NORADRENALINE

The role of the vascular endothelium in the response to a vasoconstric tor agent acting through a non-receptorial mechanism, such as KCl, was tested in the isolated mesenteric vascular bed of the rat. It was con firmed that the vasoconstrictor response evoked by stimulation of symp athetic terminals was unaffected by 100 mu N-G-nitro-D-arginine methyl ester (D-NAME), but was significantly potentiated by 100 mu M N-G-nit ro-L-arginine methyl ester (L-NAME) and by removal of endothelium. Res ponses to exogenous noradrenaline (1-100 mu M) were also enhanced by t reatment with 100 mu M N-G-monomethyl-L-arginine (L-NMMA) and with L-N AME, but not with D-NAME. The potentiating effect of NO synthesis inhi bitors was reversed by 1 mM L-arginine. Moreover, the noradrenaline-in duced vasoconstriction was significantly increased by endothelium-depr ivation. Potassium chloride (80 mM) induced a vasoconstrictor response which was not modified by pretreatment with prazosin (0.1 mu M) and y ohimbine (0.1 mu M). The response to KCl was unaffected by D-NAME (100 mu M) but the L-stereoisomer induced a significant increase in the pe rfusion pressure. In endothelium-denuded preparations the vasoconstric tor response to KCl was greater than in control conditions and was qua ntitatively similar to that observed in L-NAME-treated preparations. T he responses to electrical field stimulation, noradrenaline and KCl in endothelium-denuded preparations were not modified by L-NAME. The res ults suggest that an increase in vascular tone, per se, may represent a trigger for the release of endothelium-derived relaxing factor from endothelial cells.