S. Amerini et al., ENHANCEMENT OF THE VASOCONSTRICTOR RESPONSE TO KCL BY NITRIC-OXIDE SYNTHESIS INHIBITION - A COMPARISON WITH NORADRENALINE, Pharmacological research, 31(3-4), 1995, pp. 175-181
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.