Acetylcholine-induced vasodilation and reactive hyperemia are not affected by acute cyclo-oxygenase inhibition in human skin.
OBJECTIVE
To examine whether prostaglandins are involved in endothelium-dependent vasodilatory responses of the skin microcirculation.


METHODS
Twenty-three young male volunteers were studied on 2 different days 1-3 weeks apart. On each experimental day the forearm skin blood flow response to iontophoretically applied acetylcholine (Ach, an endothelium-dependent vasodilator) was determined with laser Doppler imaging following the intravenous administration of either the cyclo-oxygenase inhibitor lysine acetylsalicylate (L-AS), 900 mg, or the oral intake of indomethacin, 75 mg. Acetylcholine was iontophoresed both in presence and in absence of surface anesthesia. In some subjects, the effects of L-AS on skin reactive hyperemia were also assessed.


RESULTS
Acute cyclo-oxygenase inhibition with either drug influenced neither the skin blood flow response to 4 different doses of Ach (0.28, 1.4, 7, and 14 mC/cm2) nor reactive hyperemia. The peak vasodilatory response to Ach was significantly increased by skin anesthesia, regardless of whether the subjects received the cyclo-oxygenase inhibitor or not. For example, the mean response (+/-SD) to the largest dose of Ach (tested in 6 subjects, expressed in perfusion units) were as follows: in absence of anesthesia: L-AS 339 +/- 105, placebo 344 +/- 68; with anesthesia: L-AS 453 +/- 76, placebo 452 +/- 65 (p <.01 for effect of anesthesia).


CONCLUSIONS
These data give no support for a contribution of prostaglandins to acetylcholine-induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine-induced vasodilation via a prostaglandin-independent mechanism.
Dalle-Ave
Anne
A
Division of Clinical Pathophysiology and Medical Teaching, University Hospital, Lausanne, Switzerland.
Kubli
Sandrine
S
Golay
Sandrine
S
Delachaux
Anne
A
Liaudet
Lucas
L
Waeber
Bernard
B
Feihl
François
F
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced*; D007478:Iontophoresis; D008297:Male; D008833:Microcirculation; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine