Cerebrovascular responses to insulin in rats
Cerebrovascular responses to insulin in rats
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DOI：
10.1038/jcbfm.2009.177
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发表时间：
2009-12-01
影响因子：
6.3
通讯作者：
Busija, David William
中科院分区：
文献类型：
--
作者：
Katakam, Prasad Venkateswera Gurunath;Domoki, Ferenc;Busija, David William
胰岛素对脑动脉的影响从未被研究过。因此，我们测定了胰岛素在大鼠脑血管中的作用。PCR和免疫印迹研究确定胰岛素受体在脑动脉和培养的脑微血管内皮细胞（CMVEC）的表达。离体大鼠脑动脉的直径测量（%变化）显示对胰岛素的双相剂量反应，初始血管收缩为0.1 ng/mL（-9.7% +/-1.6%），随后血管舒张为1 - 100 ng/mL（31.9% +/-1.4%）。局部应用时，胰岛素还可增加体内皮质血流量（120 ng/mL时为30% +/- 8%）。清除活性氧（ROS）可消除胰岛素引起的血管收缩。内皮剥脱、K（+）通道抑制和一氧化氮（NO）合酶均能减弱胰岛素诱导的血管舒张。细胞色素P450的抑制增强血管舒张内皮完整的动脉，但促进血管收缩内皮剥脱后。抑制环氧合酶可消除所有动脉中的血管收缩，并增强血管对胰岛素的舒张作用。抑制内皮素A型受体增强血管舒张，而内皮素B型受体阻断剂减少血管舒张。体外胰岛素治疗增加脑动脉和CMVEC中Akt磷酸化。荧光研究表明，胰岛素增加细胞内钙，增加NO和ROS的产生。因此，脑血管对胰岛素的反应是由起源于内皮和平滑肌的复杂机制介导的。脑血流与代谢杂志（2009）29，1955-1967; doi：10.1038/jcbfm.2009.177; 2009年9月2日在线发表
Effects of insulin on cerebral arteries have never been examined. Therefore, we determined cerebrovascular actions of insulin in rats. Both PCR and immunoblot studies identified insulin receptor expression in cerebral arteries and in cultured cerebral microvascular endothelial cells (CMVECs). Diameter measurements (% change) of isolated rat cerebral arteries showed a biphasic dose response to insulin with an initial vasoconstriction at 0.1 ng/mL (-9.7% +/- 1.6%), followed by vasodilation at 1 to 100 ng/mL (31.9% +/- 1.4%). Insulin also increased cortical blood flow in vivo (30% +/- 8% at 120 ng/mL) when applied topically. Removal of reactive oxygen species (ROS) abolished the vasoconstriction to insulin. Endothelial denudation, inhibition of K(+) channels, and nitric oxide (NO) synthase, all diminished insulin-induced vasodilation. Inhibition of cytochrome P450 enhanced vasodilation in endothelium-intact arteries, but promoted vasoconstriction after endothelial denudation. Inhibition of cyclooxygenase abolished vasoconstriction and enhanced vasodilation to insulin in all arteries. Inhibition of endothelin type A receptors enhanced vasodilation, whereas endothelin type B receptor blockade diminished vasodilation. Insulin treatment in vitro increased Akt phosphorylation in cerebral arteries and CMVECs. Fluorescence studies of CMVECs showed that insulin increased intracellular calcium and enhanced the generation of NO and ROS. Thus, cerebrovascular responses to insulin were mediated by complex mechanisms originating in both the endothelium and smooth muscle. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1955-1967; doi:10.1038/jcbfm.2009.177; published online 2 September 2009