Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling

Abstract

Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29°C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (−14 ± 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 ± 7.7%) but did not affect the response at 30 min (−30.6 ± 9% control, −38.9 ± 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (−14.3 ± 4.2% control) to vasodilation (+26.3 ± 12.1% YP), without a significant effect on the 30-min response (−26.7 ± 6.1% YP, −43.2 ± 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction ( P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (−20.1 ± 6.4% control) to one of vasodilation (+213.4 ± 87.0% Emla), whereas the final levels did not differ significantly (−37.7 ± 10.1% control, −37.2 ± 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.