Local ascorbate administration inhibits the adrenergic vasoconstrictor response to local cooling in the human skin

Abstract

Local cooling (LC) of nonglabrous skin causes vasoconstriction via the adrenergic and removal of nitric oxide (NO) systems. Since cooling increases reactive oxygen species in smooth muscle cells and induces increased sensitivity of alpha-adrenergic receptors, antioxidant supplementation may attenuate the vasoconstrictor response to skin LC via adrenergic and/or NO systems. To test this hypothesis, we examined the effects of acute L-ascorbate (Asc, 10 mM) supplementation in human skin on the vasoconstrictor responses to LC in skin with and without NO synthase (NOS) inhibition or adrenergic receptor blockade. In a three-part study, forearm sites were instrumented with microdialysis fibers, local coolers, and laser-Doppler flow (LDF) probes in healthy volunteers. Sites were cooled from 34 to 24 degrees C at -1 degrees C/min and maintained at 24 degrees C for 20 min (parts 1 and 2) or 30 min (part 3). During the last 10 min of LC in parts 1 and 2, whole body cooling was performed to increase sympathetic vasoconstrictor activity. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to blood pressure and expressed relative to the baseline value before cooling. Treatments in each part were as follows: part 1) untreated, Asc; part 2) N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NOS, combined L-NAME + Asc; part 3) yohimbine (YOH) + propranolol (PRO) to antagonize alpha- and beta-adrenergic receptors and combined YOH + PRO + Asc. CVC reduction during LC was smaller (P < 0.001) at Asc sites (-31 +/- 4%) than at untreated sites (-56 +/- 5%). LC-induced reduction in CVC was smaller (P < 0.05) at L-NAME + Asc sites (-23 +/- 8%) than at L-NAME sites (-43 +/- 7%). LC-induced reduction in CVC did not differ between at PRO + YOH sites (-56 +/- 3%) and at PRO + YOH + Asc sites (-50 +/- 3%). These findings suggest that antioxidant supplementation inhibits the vasoconstrictor response to direct cooling through an adrenoceptor-dependent mechanism in human skin.