Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, London, United Kingdom.
J Appl Physiol (1985). 2010 Jul;109(1):11-8. doi: 10.1152/japplphysiol.01301.2009. Epub 2010 Apr 1.
A decrease in environmental temperature can directly affect the contractility of cutaneous vasculature, mediated in part by alpha(2)-adrenoceptors. Most of the cellular mechanisms underlying the cooling-enhanced contractility to alpha(2)-adrenoceptor agonists have been reported in cutaneous arteries but little information is available on cutaneous veins. To investigate the cellular mechanisms associated with the cooling-enhanced contraction to UK-14304 (alpha(2)-adrenoceptor agonist), isolated equine digital veins (EDVs) were studied at 30 degrees C and 22 degrees C. The effects of inhibitors were studied on the contractile response to UK-14304 (0.1 microM). The cooling-enhanced responses were inhibited by Rho kinase inhibitors [maximum response to UK-14304 95.2 +/- 8% of response to depolarizing Krebs solution (DKS) in control vessels cooled to 22 degrees C, compared with 31.4 +/- 6% in the presence of fasudil 1 microM and 75.8 +/- 6% with Y-27632 0.1 microM] and the effects of these inhibitors were considerably less at 30 degrees C (control response 56.4 +/- 5% of DKS; 34.9 +/- 6% with fasudil 1 microM and 50.6 +/- 9% with Y-27632 0.1 microM). Furthermore, Western blotting showed that one of the downstream targets for Rho kinase activity, ezrin/radixin/moesin, was phosphorylated after cooling and reduced by fasudil (1 microM) only at 22 degrees C. The activation of protein kinase C contributed to the contractile response, but predominantly at 30 degrees C (maximum response 82.3 +/- 9% of DKS for control; 57.7 +/- 10% in the presence of chelerythrine 10 microM) with no significant effect at 22 degrees C. The reduction of the response at 22 degrees C by antioxidants, rotenone (14% reduction), and tempol (21% reduction) suggested the contribution of reactive oxygen species (ROS). No evidence was obtained to support the participation of tyrosine kinase. These data demonstrate that Rho kinase activation and the production of ROS contributes to the cooling-enhanced contraction in these cutaneous digital veins.
环境温度的降低会直接影响皮肤血管的收缩性，这在一定程度上是通过 alpha(2)-肾上腺素能受体介导的。尽管已经有大量关于皮肤动脉中冷却增强对 alpha(2)-肾上腺素能受体激动剂收缩性的细胞机制的报道，但关于皮肤静脉的信息却很少。为了研究与 UK-14304（alpha(2)-肾上腺素能受体激动剂）冷却增强收缩相关的细胞机制，在 30°C 和 22°C 下研究了分离的马数字静脉 (EDV)。研究了抑制剂对 UK-14304（0.1 microM）收缩反应的影响。Rho 激酶抑制剂抑制冷却增强反应[最大反应至 UK-14304 在冷却至 22°C 的对照血管中为去极化 Krebs 溶液 (DKS) 反应的 95.2 +/- 8%，而在 1 microM fasudil 和 0.1 microM Y-27632 存在时为 31.4 +/- 6%，在 30°C 时效应明显较小（对照反应为 DKS 的 56.4 +/- 5%；1 microM fasudil 时为 34.9 +/- 6%，0.1 microM Y-27632 时为 50.6 +/- 9%）。此外，Western 印迹显示，Rho 激酶活性的下游靶标之一 ezrin/radixin/moesin 在冷却后发生磷酸化，仅在 22°C 时 fasudil（1 microM）可使其减少。蛋白激酶 C 的激活有助于收缩反应，但主要在 30°C 时（对照的最大反应为 DKS 的 82.3 +/- 9%；10 microM chelerythrine 存在时为 57.7 +/- 10%），在 22°C 时无显著影响。抗氧化剂鱼藤酮（减少 14%）和替米沙坦（减少 21%）在 22°C 时降低反应，表明活性氧物质（ROS）的贡献。没有证据表明酪氨酸激酶参与。这些数据表明，Rho 激酶的激活和 ROS 的产生有助于这些皮肤数字静脉的冷却增强收缩。
