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

Abstract

Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling. Am J Physiol Heart Circ Physiol 288: H1573-H1579, 2005. First published December 2, 2004; doi:10.1152/ajpheart.00849.2004.-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 (Ϫ14 Ϯ 6.6% control CVC, first 5 min) to one of vasodilation (ϩ19.7 Ϯ 7.7%) but did not affect the response at 30 min (Ϫ30.6 Ϯ 9% control, Ϫ38.9 Ϯ 6.9% bretylium; both P Ͻ 0.05, P Ͼ 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (Ϫ14.3 Ϯ 4.2% control) to vasodilation (ϩ26.3 Ϯ 12.1% YP), without a significant effect on the 30-min response (Ϫ26.7 Ϯ 6.1% YP, Ϫ43.2 Ϯ 6.5% control; both P Ͻ 0.05, P Ͼ 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P Ͼ 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (Ϫ20.1 Ϯ 6.4% control) to one of vasodilation (ϩ213.4 Ϯ 87.0% Emla), whereas the final levels did not differ significantly (Ϫ37.7 Ϯ 10.1% control, Ϫ37.2 Ϯ 8.7% Emla; both P Ͻ 0.05, P Ͼ 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.human; peripheral circulation; local control of blood flow; skin circulation; microdialysis; iontophoresis; neuropeptide Y; norepinephrine; axon reflex THE CONTROL OF SKIN BLOOD FLOW in humans involves several mechanisms. Reflex control occurs through a vasoconstrictor pathway and through an independent active vasodilator system (18, 33). These systems are both known to be sympathetic in origin. In the case of the vasoconstrictor system, the transmitters appear to be norepinephrine and one or more cotransmitters (26 -27, 36, 37, 39 -40). The active vasodilator mechanism is less well defined but appears to be cholinergic and also to involve a cotransmitter, perhaps vasoactive intestinal polypeptide (3, 21).Local thermal control of skin blood flow has also been the subject of considerable attention. Direct local warming of the skin leads to a vasodilation that involves nitric oxide and sensory nerves (20,25,38). With respect to direct local cooling, several lines of evidence point to an involvement of the sympathetic vasoconstrictor system in the reduction of skin blood flow. Postsynaptic ␣ 2 -adrenergic receptors have an enhanced affinity for norepinephrine, perhaps mediated th...

The effect of microdialysis needle trauma on cutaneous vascular responses in humans

“…The lack of effect of LA on neurogenic vasodilator function, although surprising, is in keeping with our laboratory's earlier observations of intact vasoconstrictor function following such LA treatment (11,15). Our laboratory's earlier speculation was that a greater depth of autonomic than sensory fibers may account for this observation.…”

“…LA also increased the temperature at which the onset of vasodilation occurred, possibly due to LA causing reduced nerve function and leading to decreased sensitivity to activation of the vasodilator system during whole body heat stress. Previous studies of cutaneous vascular responses to local cooling (11,15) and local heating (21) found the initiation of the local vasoconstrictor and vasodilator responses to be altered following treatment with LA. The finding that the combination of ice or LA with fiber placement reverses the increased threshold is not in keeping with this speculation about damage to nerve fibers by fiber placement.…”

“…Local temperature control at the sites of blood flow measurement was achieved with custom-designed metal Peltier cooling-heating probe holders (e.g., Refs. 1,8,10,15,35). These controlled surface temperature within 0.05°C over an area of 6.3 cm 2 with the exception of a small aperture (0.28 cm 2 ) in the center of the holder to enable placement of the laser-Doppler probe.…”

“…The use of ice before needle insertion, as a temporary anesthetic, is common but it is assumed to be sufficiently benign that the process will not affect the vascular responses. However, no work thus far has thoroughly investigated the effects of the preparatory procedures on cutaneous vascular responses.Local anesthesia (LA) is also effective in preventing the pain of fiber insertion (5,11,15,21). LA is not typically used with microdialysis fiber placement unless sensory nerve blockade is a part of the question, because the application of LA may affect the vascular responses (5,11,15,21).…”

“…LA is not typically used with microdialysis fiber placement unless sensory nerve blockade is a part of the question, because the application of LA may affect the vascular responses (5,11,15,21). Wong et al (34) recently provided evidence for an involvement of substance P in the cutaneous vascular response to whole body heat stress.…”