Central role of connexin40 in the propagation of electrically activated vasodilation in mouse cremasteric arterioles in vivo
Central role of connexin40 in the propagation of electrically activated vasodilation in mouse cremasteric arterioles in vivo
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DOI：
10.1161/01.res.0000065918.90271.9a
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发表时间：
2003-04-18
影响因子：
20.1
通讯作者：
Duling, BR
中科院分区：
文献类型：
--
作者：
Figueroa, XF;Paul, DL;Duling, BR
当刺激小动脉的一小段时，血管反应沿血管轴沿着双向传播，据称是通过缝隙连接。我们使用连接蛋白40基因敲除（Cx40（-/-））小鼠研究10秒的电刺激（30 Hz，1 ms，30至50 V）在提睾肌的第二或第三级小动脉中诱导的血管反应。在刺激部位（局部）和传导部位（上游500、1000和2000 μ m）进行测量。在野生型（Cx40（+/+））动物中，电刺激诱发局部血管收缩和传导性血管舒张，其沿血管长度沿着非常迅速地扩散而没有可检测的衰减。在Cx40（-/-）小鼠中，进行的扩张转化为血管收缩或缓慢发展的血管舒张，沿着血管长度沿着衰减。河豚毒素（TTX，1 μ mol/L）对Cx40（+/+）和Cx40（-/-）小鼠的局部血管收缩无影响，但对Cx40（+/+）动物的传导性血管舒张有增强作用。在Cx40（-/-）小鼠中，TTX在存在时消除了传导的血管收缩，并显示出随距离而衰减的小血管舒张。在Cx40（-/-）小鼠组中，电刺激引起传导性血管舒张，TTX没有影响。免疫细胞化学显示Cx40仅存在于Cx40（+/+）小鼠的小动脉内皮层中，而在Cx40（-/-）动物中该连接蛋白完全消除。这些结果表明，局灶电流刺激通过血管周围神经刺激和平滑肌激活的组合引起血管收缩。此外，电刺激激活非神经元的、Cx40依赖的血管舒张反应，该反应沿血管长度沿着传播而不衰减。
When a short segment of arteriole is stimulated, vasomotor responses spread bidirectionally along the vessel axis purportedly via gap junctions. We used connexin40 knockout ( Cx40(-/-)) mice to study vasomotor responses induced by 10-second trains of electrical stimulation ( 30 Hz, 1 ms, 30 to 50 V) in 2nd or 3rd order arterioles of the cremaster muscle. Measurements were made at the stimulation site ( local) and at conducted sites ( 500, 1000, and 2000 mum upstream). In wild-type (Cx40(+/+)) animals, electrical stimulation evoked a local vasoconstriction and a conducted vasodilation that spread very rapidly along the vessel length without detectable decay. In Cx40(-/-) mice, the conducted dilation was converted into either vasoconstriction or a slowly developing vasodilation that decayed along the vessel length. Tetrodotoxin (TTX, 1 mumol/L) had no effect on the local vasoconstriction in either Cx40(+/+) or Cx40(-/-) mice, but enhanced the conducted vasodilation in Cx40(+/+) animals. In Cx40(-/-) mice, TTX abolished the conducted vasoconstriction when present and revealed a small vasodilation that decayed with distance. In the group of Cx40(-/-) mice in which electrical stimulation elicited a conducted vasodilation, TTX had no effect. Immunocytochemistry revealed Cx40 only in the endothelial layer of arterioles from Cx40(+/+) mice and complete elimination of this connexin in the Cx40(-/-) animals. These results indicate that focal current stimulation causes vasoconstriction by a combination of perivascular nerve stimulation and smooth muscle activation. Moreover, electrical stimulation activates a nonneuronal, Cx40-dependent vasodilator response that spreads along the vessel length without decay.