Increased myogenic tone and diminished responsiveness to ATP-sensitive K+ channel openers in cerebral arteries from diabetic rats.
Increased myogenic tone and diminished responsiveness to ATP-sensitive K+ channel openers in cerebral arteries from diabetic rats.
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DOI：
10.1161/01.res.81.6.996
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发表时间：
1997-12
影响因子：
20.1
通讯作者：
Paul A. Zimmermann;H. Knot;Andra S. Stevenson;Mark Nelson
中科院分区：
文献类型：
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作者：
Paul A. Zimmermann;H. Knot;Andra S. Stevenson;Mark Nelson
糖尿病对血管，特别是内皮功能具有深远的不利影响。尽管压力引起的收缩（“肌原性紧张”）是调节血流的主要因素，但人们对糖尿病对此反应的影响知之甚少。糖尿病已被证明会减少脑动脉对合成 ATP 敏感的 K+ (KATP) 通道开放剂的扩张。在这项研究中，我们探讨了链脲佐菌素诱导的大鼠糖尿病对脑动脉（250 至 300 微米）肌源张力以及合成 KATP 通道开放剂吡那地尔和左旋卡林血管舒张的影响。血管内压力升高引起分级膜电位去极化和收缩，与正常大鼠相比，糖尿病大鼠的动脉的膜电位去极化和收缩程度更大（60 mm Hg 时，去极化多 5 mV，收缩多 22 微米）。糖尿病大鼠的加压动脉（60 mm Hg）对吡那地尔和 levcromakalim 的敏感性比对照动脉低 5 至 15 倍（糖尿病动物中吡那地尔和 levcromakalim 的 EC50 值分别为 1.4 和 0.6 mumol/L，对照动物中分别为 0.3 和 0.04；P < .05）。在对照动脉中去除内皮或添加 NO 合酶抑制剂 NG-硝基-L-精氨酸 (LNNA) 会降低对 KATP 通道开放剂的敏感性，并使对照动脉去极化和收缩至与糖尿病动物动脉中观察到的水平相似的水平。硝普钠引起膜电位超极化并增强糖尿病动物动脉中对吡那地尔的反应。去除内皮或 LNNA 对糖尿病动物的表观 KATP 通道开放剂敏感性、膜电位和压力诱导的动脉收缩几乎没有影响。结果与以下假设一致：这种类型的糖尿病会导致内皮细胞强直性 NO 释放减少，进而导致膜电位去极化和血管收缩，从而导致对 KATP 通道开放剂的反应减弱。
Diabetes mellitus has profound adverse effects on vascular and, in particular, endothelial function. Although pressure-induced constriction ("myogenic tone") is a major contributor to the regulation of blood flow, little is known about the effects of diabetes on this response. Diabetes has been shown to diminish the dilation of cerebral arteries to synthetic ATP-sensitive K+ (KATP) channel openers. In this study, we explored the effects of diabetes induced in rats by streptozotocin on cerebral artery (250 to 300 microns) myogenic tone and on vasodilations to the synthetic KATP channel openers pinacidil and levcromakalim. Elevation of intravascular pressure caused a graded membrane potential depolarization and constriction, which was greater in arteries from diabetic rats compared with normal rats (at 60 mm Hg, 5 mV more depolarized and 22 microns more constricted). Pressurized arteries (at 60 mm Hg) from diabetic rats were 5- to 15-fold less sensitive to pinacidil and levcromakalim than were control arteries (EC50 values for pinacidil and levcromakalim were 1.4 and 0.6 mumol/L, respectively, in diabetic animals and 0.3 and 0.04, respectively, in control animals; P < .05). Removal of the endothelium or addition of a NO synthase inhibitor, NG-nitro-L-arginine (LNNA), in control arteries decreased the sensitivity to KATP channel openers and depolarized and constricted control arteries to levels similar to those observed in arteries from diabetic animals. Sodium nitroprusside caused a membrane potential hyperpolarization and enhanced the response to pinacidil in arteries from diabetic animals. Removal of the endothelium or LNNA had little effect on the apparent KATP channel opener sensitivity, the membrane potential, and pressure-induced constrictions of arteries from diabetic animals. The results are consistent with the hypothesis that this type of diabetes leads to a decrease in tonic NO release from the endothelium, which in turn causes membrane potential depolarization and vasoconstriction, resulting in a diminished response to KATP channel openers.