The role of nitric oxide in the cutaneous vasoconstrictor response to local cooling

Cutaneous blood flow (CBF) declines in response to local cooling (LC), which is in part adrenergically dependent. Previous work indicates that the remainder of the vasoconstrictor response to LC may be through an effect on nitric oxide synthase (NOS) activity. To determine the influence of NOS and adrenergic function on the vasoconstrictor response in skin, we assessed the response to LC with NOS inhibition (NG‐nitro‐L‐arginine methyl ester; L‐NAME), with and without bretylium (BT) pre‐treatment. In 6 (5 male, 1 female) subjects forearm CBF was monitored by laser‐Doppler flowmetry. Control of local skin and body temperature was achieved with Peltier cooler/heater probe holders and water perfused suits, respectively. Microdialysis fibers were inserted aseptically. Saline and L‐NAME were infused by microdialysis. BT was administered by iontophoresis. Cutaneous vascular conductance (CVC) was calculated from CBF and blood pressure. There were four experimental sites; site 1 acted as a control, and site 2 was pre‐treated with BT, both had saline infused. Sites 3 and 4 had L‐NAME infused, site 4 was pre‐treated with BT. All four sites had slow (−0.33°C · min‐1) LC (34 ‐ 24°C) for 35 min. In response to LC, CVC at the control site decreased 68±4%, and 39±5% at the BT treated site (P < 0.05). The infusion of L‐NAME elicited a 35±4% decrease at the L‐NAME and BT+L‐NAME sites (P < 0.05). LC caused a further 23±5% of initial baseline decrease in CVC at the L‐NAME site (P < 0.05); however, the BT+L‐NAME site was unaffected by the LC (P > 0.05). These data suggest that the vasoconstriction with slow LC is a combination of increased adrenergic tone and decreased activity of NOS. (NIH HL059166)