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大鼠眼动脉在急性高糖暴露及II型糖尿病模型中的肌源性张力和反应性

Myogenic tone and reactivity of rat ophthalmic artery in acute exposure to high glucose and in a type II diabetic model.

作者信息

Ito Isamu, Jarajapu Yagna P R, Guberski Dennis L, Grant Maria B, Knot Harm J

机构信息

Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL, USA.

出版信息

Invest Ophthalmol Vis Sci. 2006 Feb;47(2):683-92. doi: 10.1167/iovs.05-1012.

Abstract

PURPOSE

To evaluate the effect of acute exposure to high glucose on myogenic tone and reactivity of the rat ophthalmic artery and to compare the observations with that in ophthalmic artery from a diabetic rat model.

METHODS

Ophthalmic arteries from Sprague-Dawley rats were pressurized at 70 mmHg in an arteriograph, and outer diameter was monitored. Myogenic tone was assessed over a range of intraluminal pressures in the presence and absence of high glucose or mannitol. The effects of high glucose on reactivity to carbachol and phenylephrine were determined. Arteries from type II diabetic BBZDR/Wor rats and age-matched control rats were evaluated for myogenic tone and reactivity.

RESULTS

Myogenic tone was enhanced by 25 mM, but decreased by 40 mM, glucose and was not affected by mannitol. Constriction to phenylephrine was not affected by 25 mM, but was decreased by 40 mM glucose, and carbachol-mediated dilation was unaffected. Effects of high glucose were not observed in the absence of endothelium. Miconazole, a nonselective inhibitor of cytochrome-P450 enzymes or dihydro-ouabain, an inhibitor of Na+,K+-ATPase blocked the effect of 40 mM but not 25 mM glucose. Arteries from diabetic rats showed decreased myogenic tone compared with control arteries, and this decrease was not observed in the absence of endothelium.

CONCLUSIONS

Acute exposure to high glucose has a concentration- and endothelium-dependent effect on the myogenic tone of rat ophthalmic artery. Attenuation of tone by high glucose is probably due to the activation of smooth muscle Na+,K+-ATPase by endothelial cytochrome-P450 metabolite. Pressure-mediated autoregulation in ophthalmic artery in type II diabetic BBZDR/Wor rat operates at lower resistance, probably due to hyperglycemia.

摘要

目的

评估急性高糖暴露对大鼠眼动脉肌源性张力和反应性的影响,并将观察结果与糖尿病大鼠模型眼动脉的情况进行比较。

方法

将来自斯普拉格-道利大鼠的眼动脉在血管造影仪中加压至70 mmHg,并监测外径。在有或无高糖或甘露醇存在的情况下,在一系列管腔内压力范围内评估肌源性张力。测定高糖对卡巴胆碱和去氧肾上腺素反应性的影响。对II型糖尿病BBZDR/Wor大鼠和年龄匹配的对照大鼠的动脉进行肌源性张力和反应性评估。

结果

25 mM葡萄糖可增强肌源性张力,但40 mM葡萄糖则使其降低,甘露醇对其无影响。25 mM葡萄糖对去氧肾上腺素的收缩作用无影响,但40 mM葡萄糖使其降低,卡巴胆碱介导的舒张作用不受影响。在无内皮的情况下未观察到高糖的作用。咪康唑(一种细胞色素P450酶的非选择性抑制剂)或二氢哇巴因(一种Na +,K + -ATP酶抑制剂)可阻断40 mM而非25 mM葡萄糖的作用。与对照动脉相比,糖尿病大鼠的动脉肌源性张力降低,在无内皮的情况下未观察到这种降低。

结论

急性高糖暴露对大鼠眼动脉的肌源性张力具有浓度和内皮依赖性作用。高糖导致的张力减弱可能是由于内皮细胞色素P450代谢产物激活了平滑肌Na +,K + -ATP酶。II型糖尿病BBZDR/Wor大鼠眼动脉的压力介导的自身调节在较低阻力下发挥作用,可能是由于高血糖所致。

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