Recovery of nitric oxide from acetylcholine-mediated vasodilatation in human skin in vivo.
OBJECTIVE
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 (approximately 30%) the ACh-induced increase in blood flux. At concentrations > or =6.25 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 H1 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.
Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, UK.
Paraskevi
P
Boutsiouki
Sophia
S
Georgiou
Geraldine F
GF
Clough
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001369:Axons; D003956:Dialysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000032:analysis; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis* / Q000502:physiology; D011537:Pruritus; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000294:innervation; D014664:Vasodilation / Q000187:drug effects*
D009569:Nitric Oxide; D006632:Histamine; D000109:Acetylcholine