Submitted on August 30, 2006
Accepted on November 16, 2006
Cerebral Vascular Dysfunction in TallyHo Mice: A New
Model of Type II Diabetes
Sean P Didion1*, Cynthia M. Lynch2, and Frank M. Faraci3
1 Internal Medicine, University of Iowa, Iowa City, Iowa, United States
2 Iowa City, Iowa, United States; Internal Medicine, University of Iowa, Iowa City, Iowa, United States
3 Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City, Iowa, United States
* To whom correspondence should be addressed. E-mail: sean-didion{at}uiowa.edu.
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 using a cranial window and in vitro using tissue baths, respectively. Dilatation of cerebral arterioles (baseline diameter = 33± µm) in response to acetylcholine (ACh), but not to nitroprusside, was markedly reduced (P<0.05) in TallyHo mice. Responses of cerebral arterioles to ACh in TallyHo mice were restored to normal with polyethylene-glycol superoxide dismutase (PEG-SOD, 100 U/ml; a superoxide scavenger). Responses to Ach were also greatly impaired (P<0.05) in carotid arteries from TallyHo mice. Phenylephrine- (PE) and serotonin- (5-HT), but not to KCl- or U46619-, induced contraction was increased 2-4 fold (P<0.05) in carotid arteries of TallyHo mice. Responses to PE and 5-HT were reduced to similar levels in the presence of Y-27632 (an inhibitor of Rho-kinase; 3 µmol/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.
