Contributions of endothelial nitric oxide synthase, noradrenaline, and neuropeptide Y to local warming-induced cutaneous vasodilatation in men

• Sympathetic nerves are required for vasodilation in response to local skin warming.
• Noradrenaline and neuropeptide Y act through eNOS to elicit vasodilatation.
• eNOS is significantly involved in mediating the cutaneous vasodilator response to skin warming.
• Data indicate a relationship between sympathetic nerves and the endothelium.

We performed a two-part study to determine the roles of endothelial nitric oxide synthase (eNOS) and the vasoconstrictor nerves neurotransmitters noradrenaline (NA) and neuropeptide Y (NPY) in the cutaneous vasodilator response to local skin warming. Forearm skin sites were instrumented with intradermal microdialysis fibres, local heaters, and laser-Doppler flow (LDF) probes. Sites were locally heated from 34 to 42 °C. LDF was expressed as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). In Part I, we tested whether sympathetic noradrenergic nerves acted via eNOS. In 8 male participants, treatments were as follows: 1) untreated; 2) bretylium tosylate (BT), preventing sympathetic neurotransmitter release; 3) l-NAA to inhibit eNOS; and 4) combined BT + l-NAA. At treated sites, the initial peak response was markedly reduced, and the plateau phase response to 35 min of local warming was also reduced (P < 0.05), which was not different among those sites (P > 0.05). In Part II, we tested whether NA and NPY were involved in the vasodilator response to local warming. In Part IIa, treatments were: 1) untreated; 2) propranolol and yohimbine to antagonize α- and β-receptors; 3) l-NAA; and 4) combined propranolol, yohimbine, and l-NAA. In Part IIb, conditions were: 1) untreated; 2) BIBP to antagonize Y1-receptors; 3) l-NAA; and 4) combined BIBP and l-NAA. All treatments caused a reduction in the initial peak and plateau responses to local skin warming (P < 0.05). The results of Part II indicate that both NA and NPY play roles in the cutaneous vasodilator response and their actions are achieved via eNOS. These data indicate that NA and NPY are involved in the initial, rapid rise in skin blood flow at the onset of local skin warming. However, their vasodilator actions in response to local skin warming appears to be manifested through eNOS.