Insulin resistance does not impair contractile responses of cerebral arteries
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- 作者：Steve A. Simandle ; Benedek Erdö ; s ; James A. Snipes ; Allison W. Miller and David W. Busija
- 关键词：Insulin resistance ; Endothelin ; Cerebral arteries
- 刊名：Life Sciences
- 出版年：2005
- 出版时间：2005
- 年：2005
- 卷：77
- 期：18
- 页码：2262-2272
- 全文大小：130 K
文摘
Insulin resistance (IR) impairs endothelium-mediated vasodilation in cerebral arteries as well as K+ channel function in vascular smooth muscle. Peripheral arteries also show an impaired endothelium-dependent vasodilation in IR and concomitantly show an enhanced contractile response to endothelin-1 (ET-1). However, the contractile responses of the cerebral arteries in IR have not been examined systematically. This study examined the contractile responses of pressurized isolated middle cerebral arteries (MCAs) in fructose-fed IR and control rats. IR MCAs showed no difference in pressure-mediated (80 mmHg) vasoconstriction compared to controls, either in time to develop spontaneous tone (control: 61 ± 3 min, n = 30; IR: 63 ± 2 min, n = 26) or in the degree of that tone (control: 60 min: 33 ± 2 % , n = 22 vs. IR 60 min: 34 ± 3 % , n = 17). MCAs treated with ET-1 (10− 8.5 M) constrict similarly in control (53 ± 3 % , n = 14) and IR (53 ± 3 % , n = 14) arteries. Constrictor responses to U46619 (10− 6 M) are also similar in control (48 ± 9 % , n = 8) and IR (42 ± 5 % , n = 6) MCAs as are responses to extraluminal uridine 5′-triphosphate (UTP; 10− 4.5 M) (control: 35 ± 7 % , n = 11 vs. IR: 38 ± 3 % , n = 10). These findings demonstrate that constrictor responses remain intact in IR despite a selective impairment of dilator responses and endothelial and vascular smooth muscle K+ channel function in cerebral arteries. Thus, it appears that the increased susceptibility to cerebrovascular abnormalities associated with IR and diabetes (including cerebral ischemia, stroke, vertebrobasilar transient ischemic attacks) is not due to an enhanced vasoreactivity to constrictor agents.