Silent α2C-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries
Silent α2C-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries
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DOI：
10.1152/ajpheart.2000.278.4.h1075
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发表时间：
2000-04-01
影响因子：
4.8
通讯作者：
Flavahan, NA
中科院分区：
文献类型：
--
作者：
Chotani, MA;Flavahan, S;Flavahan, NA
寒冷通过增加平滑肌α（2）-肾上腺素能受体（α（2）-AR）的反应性来收缩皮肤血管。进行实验以确定α（2）-AR亚型（α（2A-）、α（2B-）、α（2C-）ARS）在该应答中的作用。用苯肾上腺素刺激α（1）-AR或用UK-14，304刺激α（2）-AR可引起安装在加压肌描记系统中的离体小鼠尾动脉收缩。与近端动脉相比，远端动脉对aa-AR激活的反应更强，但对α（1）-AR激活的反应较弱。冷增强了远端动脉对α（2）-AR激活的收缩，但不影响对α-AR刺激的反应或肌源性张力水平。蛋白质印迹分析表明，α（2A-）和α（2C-）AR在尾动脉中的表达：与近端动脉相比，α（2C）-AR的表达在远端动脉中减少，而α（2A）-AR的糖基化形式的表达在远端动脉中增加。在37 ℃时，α（2）-AR诱导的远端动脉血管收缩可通过选择性阻断α（2A）-ARS（BRL-44408）而非选择性抑制α（2B）-AR（ARC-239）或α（2C）-AR（MK-912）来抑制。相比之下，在冷暴露（28 ℃）期间，对UK-14，304的增强反应被α（2C）-AR拮抗剂MK-912抑制，其选择性地消除了冷诱导的反应放大。这些实验表明，低温诱导的α（2）-AR扩增是由这些皮肤动脉中通常沉默的α（2C）-AR介导的。阻断α（2C）-AR可能是治疗雷诺现象的有效方法。
Cold constricts cutaneous blood vessels by increasing the reactivity of smooth muscle alpha(2)-adrenergic receptors (alpha(2)-ARs). Experiments were performed to determine the role of alpha(2)-AR subtypes (alpha(2A-), alpha(2B-), alpha(2C-)ARS) in this response. Stimulation of alpha(1)-ARs by phenylephrine or alpha(2)-ARs by UK-14,304 caused constriction of isolated mouse tail arteries mounted in a pressurized myograph system. Compared with proximal arteries, distal arteries were more responsive to aa-AR activation but less responsive to activation of alpha(1)-ARs. Cold augmented constriction to alpha(2)-AR activation in distal arteries but did not affect the response to al-AR stimulation or the level of myogenic tone. Western blot analysis demonstrated expression of a(2A-) and alpha(2C-)ARs in tail arteries: expression of alpha(2C)-ARs decreased in distal compared with proximal arteries, whereas expression of the glycosylated form of the alpha(2A)-AR increased in distal arteries. At 37 degrees C, alpha(2)-AR-induced vasoconstriction in distal arteries was inhibited by selective blockade of alpha(2A)-ARS (BRL-44408) but not by selective inhibition of alpha(2B)-ARs (ARC-239) or alpha(2C)-ARs (MK-912). In contrast, during cold exposure (28 degrees C), the augmented response to UK-14,304 was inhibited by the alpha(2C)-AR antagonist MK-912, which selectively abolished cold-induced amplification of the response. These experiments indicate that cold-induced amplification of alpha(2)-ARs is mediated by alpha(2C)-ARs that are normally silent in these cutaneous arteries. Blockade of alpha(2C)-ARs may prove an effective treatment for Raynaud's Phenomenon.