Role of alpha2C-adrenoceptors in the reduction of skin blood flow induced by local cooling in mice.

BACKGROUND AND PURPOSE: The reduction of skin blood flow induced by local cooling results from a reflex increase in sympathetic output and an enhanced vasoconstrictor activity of cutaneous vessels. The present study investigated the latter local response in vivo in tetrodotoxin-treated mice, in which the sympathetic nerve tone was abolished. EXPERIMENTAL APPROACH: Male ddY mice, anaesthetized with pentobarbitone, were treated with tetrodotoxin and artificially ventilated. The plantar skin blood flow (PSBF) was measured by laser Doppler flowmetry. KEY RESULTS: Cooling the air temperature around the left foot from 25 to 10 degrees C decreased the PSBF of the left foot. Bunazosin, an alpha (1)-adrenoceptor antagonist, RS79948, an alpha (2)-adrenoceptor antagonist, and MK-912, an alpha (2C)-adrenoceptor antagonist, all significantly inhibited the cooling-induced reduction of PSBF; the inhibition by bunazosin was relatively small compared with that by RS79948 and MK-912. The response was not affected by guanethidine or bretylium, but was diminished in adrenalectomized mice. An intra-arterial injection of clonidine, an alpha (2)-adrenoceptor agonist, to the left iliac artery of adrenalectomized mice caused a transient decrease in PSBF, which was significantly augmented at 10 degrees C. MK-912 suppressed only the augmented portion at 10 degrees C. Y-27632, H-1152 and fasudil, Rho kinase inhibitors, also inhibited the cooling-induced reduction of PSBF. RS79948 caused no further reduction of the cooling-induced response after the inhibition by Y-27632. CONCLUSIONS AND IMPLICATIONS: Local cooling-induced reduction of skin blood flow in mice primarily results from increased reactivity of alpha (2C)-adrenoceptors to circulating catecholamines, in which the Rho/Rho kinase pathway is involved.