Recovery of nitric oxide from acetylcholine-mediated vasodilatation in human skin in vivo

Objectives: To investigate the relative contribution of nitric oxide ( NO) to the vascular and neural mechanisms underlying the ACh-induced vasodilatation in human skin. Methods: ACh was delivered to the skin of the forearm of 28 healthy volunteers using intradermal microdialysis. Subsequent changes in tissue levels of NO and histamine were measured in the dialysate outflow and the associated changes in skin blood flux followed with the use of scanning laser Doppler imaging. Results: ACh caused a dose-dependent increase in skin blood flux measured directly above the probe, associated with a twofold increase in dialysate NO. L-NAME (5 mM) delivered simultaneously via the dialysis probe totally blocked the increase in dialysate NO but only partially attenuated (similar to30%) the ACh-induced increase in blood flux. At concentrations greater than or equal to6.25 mM, ACh also induced a widespread flare response, up to 40 mm in width, accompanied by the sensation of itch. The flare was not blocked by L-NAME or the H-1 receptor antagonist levocetirizine, but was reduced by C-fiber blockade. Dialysate histamine levels remained unchanged at all times. Conclusions: These experiments offer further insight into the use of dialysis as an experimental technique in the skin. They provide direct evidence that the skin microvascular response to ACh is only partially mediated by NO. Further they suggest that ACh at higher concentrations can induce an axon-reflex-mediated response that is independent of NO release at the site of dermal provocation or of local histamine release.