Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes
Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes
复制标题
DOI：
10.1152/ajpheart.00939.2006
复制
发表时间：
2007-03-01
影响因子：
4.8
通讯作者：
Faraci, Frank M.
中科院分区：
文献类型：
--
作者：
Didion, Sean P.;Lynch, Cynthia M.;Faraci, Frank M.
本研究的目的是表征血管反应，并检查TallyHo小鼠血管功能障碍的机制，一种新的II型糖尿病多基因模型。分别在活体和离体条件下，用颅窗法和组织浴法检测脑小动脉和颈动脉的反应。在TallyHo小鼠中，对乙酰胆碱反应的脑小动脉扩张（基线直径= 33 +/- 1 μ m）显著减少（P < 0.05），但对硝普钠反应不明显。用聚乙二醇-超氧化物歧化酶（100 U/ ml;超氧化物清除剂）使TallyHo小鼠脑小动脉对乙酰胆碱的反应恢复正常。TallyHo小鼠颈动脉对乙酰胆碱的反应也明显受损（P < 0.05）。在TallyHo小鼠的颈动脉中，苯丙氨酸和5-羟色胺诱导的收缩增加了2 - 4倍（P < 0.05），但KCl或U46619诱导的收缩没有增加。在Y- 27632（Rho激酶抑制剂; 3 μ mol/l）存在下，对苯丙氨酸和5-羟色胺的反应降低至相似水平。这些发现首次证明TallyHo小鼠存在血管功能障碍，并且氧化应激和Rho激酶活性增强可能导致该II型糖尿病遗传模型中血管功能的改变。
The purpose of this study was to characterize vascular responses and to examine mechanisms of vascular dysfunction in TallyHo mice, a new polygenic model of Type II diabetes. Responses of cerebral arterioles and carotid arteries were examined in vivo by using a cranial window and in vitro by using tissue baths, respectively. Dilatation of cerebral arterioles ( baseline diameter = 33 +/- 1 mu m) in response to acetylcholine, but not to nitroprusside, was markedly reduced ( P < 0.05) in TallyHo mice. Responses of cerebral arterioles to acetylcholine in TallyHo mice were restored to normal with polyethylene glycol- superoxide dismutase ( 100 U/ ml; a superoxide scavenger). Responses to acetylcholine were also greatly impaired ( P < 0.05) in the carotid arteries from TallyHo mice. Phenylephrine- and serotonin-, but not to KCl- or U46619-, induced contraction was increased two- to fourfold ( P < 0.05) in carotid arteries of TallyHo mice. Responses to phenylephrine and serotonin were reduced to similar levels in the presence of Y- 27632 ( an inhibitor of Rho kinase; 3 mu mol/l). These findings provide the first evidence that vascular dysfunction is present in TallyHo mice and that oxidative stress and enhanced activity of Rho kinase may contribute to altered vascular function in this genetic model of Type II diabetes.