Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin.
Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin.
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DOI：
10.1152/ajpheart.01078.2006
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发表时间：
2007-04
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影响因子：
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通讯作者：
Caitlin S. Thompson-Torgerson;Lacy A. Holowatz;N. Flavahan;W. Kenney
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作者：
Caitlin S. Thompson-Torgerson;Lacy A. Holowatz;N. Flavahan;W. Kenney
皮肤血管收缩（VC）是对冷暴露的初始温度调节反应，可以通过全身或局部皮肤冷却引起。然而，局部冷诱导VC的机制还不清楚。我们测试的假设，Rho激酶参与局部冷诱导的皮肤VC。在7名男性和女性（20 - 27岁）中，多达4个前臂腹侧皮肤部位装有皮内微透析纤维，用于冷却期间的局部药物递送。在每个部位用激光多普勒血流仪监测皮肤血流，同时降低局部皮肤温度并维持在24 ℃ 40 min。皮肤血管传导性（CVC;激光多普勒血流仪/平均动脉压）表示为相对于34 ℃基线的百分比变化。在冷却的前5分钟，对照部位的CVC降低（乳酸林格氏液）至-45 +/-6%（P <0.001），在肾上腺素受体拮抗部位增加（育亨宾+普萘洛尔）至15 +/-14%（P = 0.002），在Rho激酶抑制（法舒地尔）和肾上腺素受体拮抗+Rho激酶抑制位点均保持不变（育亨宾+普萘洛尔+法舒地尔）（分别为-9 +/-1%，P = 0. 4和-6 +/-2%，P = 0. 4）。在冷却的最后5分钟内，与基线值相比，所有部位的CVC进一步降低（对照组：-77 +/-4%，P <0.001;肾上腺素受体拮抗组：-61 +/-3%，P <0.001; Rho激酶抑制组：-34 +/-7%，P <0.001;肾上腺素受体拮抗+Rho激酶抑制位点，-35 ± 3%，P <0.001）。Rho激酶抑制组和联合治疗组与肾上腺素受体拮抗组和对照组比较，均有显著性差异（P <0.0001）。Rho激酶介导早期和晚期冷诱导VC，支持体外研究结果，并提供了一个假定的机制，通过该机制，肾上腺素能和非肾上腺素能冷诱导VC发生在体内人体体温调节模型。
Cutaneous vasoconstriction (VC) is the initial thermoregulatory response to cold exposure and can be elicited through either whole body or localized skin cooling. However, the mechanisms governing local cold-induced VC are not well understood. We tested the hypothesis that Rho kinase participates in local cold-induced cutaneous VC. In seven men and women (20-27 yr of age), up to four ventral forearm skin sites were instrumented with intradermal microdialysis fibers for localized drug delivery during cooling. Skin blood flow was monitored at each site with laser-Doppler flowmetry while local skin temperature was decreased and maintained at 24 degrees C for 40 min. Cutaneous vascular conductance (CVC; laser-Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34 degrees C baseline. During the first 5 min of cooling, CVC decreased at control sites (lactated Ringer solution) to -45 +/- 6% (P < 0.001), increased at adrenoceptor-antagonized sites (yohimbine + propranolol) to 15 +/- 14% (P = 0.002), and remained unchanged at both Rho kinase-inhibited (fasudil) and adrenoceptor-antagonized + Rho kinase-inhibited sites (yohimbine + propranolol + fasudil) (-9 +/- 1%, P = 0.4 and -6 +/- 2%, P = 0.4, respectively). During the last 5 min of cooling, CVC further decreased at all sites when compared with baseline values (control, -77 +/- 4%, P < 0.001; adrenoceptor antagonized, -61 +/- 3%, P < 0.001; Rho kinase inhibited, -34 +/- 7%, P < 0.001; and adrenoceptor antagonized + Rho kinase inhibited sites, -35 +/- 3%, P < 0.001). Rho kinase-inhibited and combined treatment sites were significantly attenuated when compared with both adrenoceptor-antagonized (P < 0.01) and control sites (P < 0.0001). Rho kinase mediates both early- and late-phase cold-induced VC, supporting in vitro findings and providing a putative mechanism through which both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human thermoregulatory model.