Acetylcholine-Induced Vasodilation and Reactive Hyperemia are not Affected by Acute Cyclo-Oxygenase Inhibition in Human Skin

Abstract

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.