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Am J Physiol Heart Circ Physiol (June 23, 2006). doi:10.1152/ajpheart.00389.2006
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Submitted on April 12, 2006
Accepted on June 13, 2006

High Fat Diet-Induced Reduction in Nitric Oxide-Dependent Arteriolar Dilation in Rats. Role of Xanthine Oxidase-Derived Superoxide Anion

Nora Erdei1, Attila Toth1, Eniko T Pasztor2, Zoltan Papp2, Istvan Edes2, Akos Koller3, and Zsolt Bagi2*

1 Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary
2 Debrecen, Hungary; Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary
3 Department of Physiology, New York Medical College, Valhalla, New York, United States

* To whom correspondence should be addressed. E-mail: bagizs{at}jaguar.unideb.hu.

Obesity leads to dysfunction of resistance arteries, which may contribute to the development of hypertension. We hypothesized that high fat diet-induced obesity impairs the endothelium-dependent dilation of arterioles. Male Wistar rats were fed with normal (control) or HFD (60 % of fat, for 10 weeks). In rats with HFD, body weight, mean arterial blood pressure, serum insulin, cholesterol, and glucose were elevated. In isolated gracilis muscle arterioles (~160 µm) of HFD rats dilations to ACh (max:83±3%) and histamine (16±4%) were significantly decreased compared to those of control responses (90±2% and 46±4%, respectively). Dilations to the NO donor, sodium nitroprusside were similar in the two groups. Inhibition of NO synthesis by L-NAME reduced ACh- and histamine-induced dilations in control arterioles, but had no effect on microvessels of HFD rats. The superoxide dismutase mimetic, Tiron or xanthine oxidase inhibitor, allopurinol enhanced ACh- (90±2% and 93±2%, respectively) and histamine-induced dilations (30±7% and 37±8%, respectively) in HFD arterioles, whereas the NAD(P)H oxidase inhibitor, apocynin had no significant effect. Correspondingly, in carotid arteries of HFD rats an enhanced superoxide production was shown by lucigenin chemiluminescense, in association with an increased xanthine oxidase, but not NAD(P)H oxidase activity. In addition, a marked xanthine oxidase immunostaining was detected in the endothelial layer of the gracilis arterioles of HFD, but not in control rats. These findings suggest that in obese rats NO-mediation of endothelium-dependent dilation of skeletal muscle arterioles is reduced due to an enhanced xanthine oxidase-derived superoxide production.




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