Honda M, Suzuki M, Nakayama K, Ishikawa T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
Br J Pharmacol. 2007 Sep;152(1):91-100. doi: 10.1038/sj.bjp.0707380. Epub 2007 Jul 9.
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.
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.
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.
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.
局部冷却引起的皮肤血流减少是交感神经输出反射性增加以及皮肤血管血管收缩活性增强所致。本研究在经河豚毒素处理的小鼠体内研究了后者的局部反应，在这些小鼠中交感神经张力被消除。
用戊巴比妥麻醉的雄性ddY小鼠，经河豚毒素处理并进行人工通气。通过激光多普勒血流仪测量足底皮肤血流（PSBF）。
将左脚周围的空气温度从25℃降至10℃可降低左脚的PSBF。α（1）-肾上腺素能受体拮抗剂布那唑嗪、α（2）-肾上腺素能受体拮抗剂RS79948和α（2C）-肾上腺素能受体拮抗剂MK-912均显著抑制冷却诱导的PSBF降低；与RS79948和MK-912相比，布那唑嗪的抑制作用相对较小。该反应不受胍乙啶或溴苄铵的影响，但在肾上腺切除的小鼠中减弱。向肾上腺切除小鼠的左髂动脉内注射α（2）-肾上腺素能受体激动剂可乐定可导致PSBF短暂降低，在10℃时显著增强。MK-912仅抑制10℃时增强的部分。Rho激酶抑制剂Y-27632、H-1152和法舒地尔也抑制冷却诱导的PSBF降低。在Y-27632抑制后，RS79948未进一步降低冷却诱导的反应。
小鼠局部冷却诱导的皮肤血流减少主要是由于α（2C）-肾上腺素能受体对循环儿茶酚胺的反应性增加，其中涉及Rho/Rho激酶途径。
