Nitric oxide and neurally mediated regulation of skin blood flow during local heating

The mechanisms underlying the skin blood flow (SkBF) response to local heat ing are complex and poorly understood. Our goal was to examine the role of axon reflexes and nitric oxide (NO) in the SkBF response to a local heating protocol. We performed 40 experiments following a standardized heating pro tocol with different interventions, including blockade of the axon reflex ( EMLA cream), antebrachial nerve blockade (0.5% bupivacaine injection), and NO synthase (NOS) inhibition (greater than or equal to 10 mM N-G-nitro-L-ar ginine methyl ester; microdialysis). Appropriate controls were performed to verify the efficacy of the various blocks. Values are expressed as a perce ntage of maximal SkBF (SkBF(max); 50 mM sodium nitroprusside). At the initi ation of local heating, SkBF rose to an initial peak, followed by a brief n adir, and a secondary, progressive rise to a plateau. Axon reflex block dec reased the initial peak from 75+3 to 32 +/- 2% SkBF(max) (P < 0.01 vs. cont rol) but did not affect the plateau. NOS inhibition before and throughout l ocal heating reduced the initial peak from 75 +/- 3 to 56 +/- 3% SkBF(max) (P < 0.01) and the plateau from 87 +/- 4 to 40 +/- 5%. NOS inhibition durin g axon reflex block did not further reduce the initial SkBF peak compared w ith axon reflex block alone. Antebrachial nerve block did not affect the lo cal heating SkBF response. The primary finding of these studies is that the re are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating: a fast-responding vasodilator system medi ated by the axon reflexes and a more slowly responding vasodilator system t hat relies on local production of NO.