Effect of endothelium on the actions of sympathetic and sensory nerves in the perfused rat mesentery.

We and others have previously demonstrated that pretreatment with capsaicin produces an augmentation of vasoconstrictor responses to transmural nerve stimulation. In the present study, removal of endothelium by saponin or inhibition of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester produced an augmentation of vasoconstrictor responses to transmural nerve stimulation, responses which were further potentiated after treatment with capsaicin to desensitize sensory nerves. Capsaicin treatment decreased vasodilator responses to acetylcholine, but only at low acetylcholine concentrations. Potentiation by capsaicin of vasoconstrictor responses to transmural nerve stimulation was not affected by indomethacin. In the presence of guanethidine and methoxamine, transmural nerve stimulation caused vasodilator responses in the perfused rat mesentery. These responses were unaffected by removal of endothelium, as were vasodilator responses to exogenous calcitonin gene-related peptide (CGRP). In contrast, substance P did not produce any relaxation in the methoxamine-contracted mesentery. This study suggests that facilitation of vasoconstrictor responses to transmural nerve stimulation after capsaicin treatment primarily reflects inhibition of sensory nerve effects resulting in an increase of sympathetic vasoconstrictor actions. The present results also suggest that vasodilator responses to sensory nerve activation or exogenous CGRP are endothelium-independent and that substance P does not significantly contribute to modulation of vascular tone in the rat mesentery.