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 venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through α‐adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser‐Doppler flowmetry over sites following local administration of terazosin (α1‐antagonist), yohimbine (α2‐antagonist), phentolamine (non‐selective α‐antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 ± 1 cm below the heart. The arm remained in this position for 2 min. Selective and non‐selective α‐adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering α‐adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non‐adrenergic, but neurally mediated, local mechanism.