| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
T. Pásztor,11Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, 2Department of Pathophysiology, Semmelweis University, Budapest, Hungary; and 3Department of Physiology, New York Medical College, Valhalla, New York
Submitted 12 April 2006 ; accepted in final form 13 June 2006
Obesity frequently leads to the development of hypertension. We hypothesized that high-fat diet (HFD)-induced obesity impairs the endothelium-dependent dilation of arterioles. Male Wistar rats were fed with normal (control) or HFD (60% of saturated fat, for 10 wk). In rats with HFD, body weight, mean arterial blood pressure, and serum insulin, cholesterol, and glucose were elevated. In isolated gracilis muscle arterioles (diameter: 
160 µm) of HFD, rat dilations to ACh (at 1 µM, maximum: 83 ± 3%) and histamine (at 10 µM, maximum: 16 ± 4%) were significantly (P < 0.05) decreased compared with those of control responses (maximum: 90 ± 2 and 46 ± 4%, respectively). Dilations to the NO donor sodium nitroprusside were similar in the two groups. Inhibition of NO synthesis by N
-nitro-L-arginine methyl ester 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 (maximum: 90 ± 2 and 93 ± 2%, respectively)- and histamine (maximum: 30 ± 7 and 37 ± 8%, respectively)-induced dilations 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-enhanced chemiluminescence, 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 because of an enhanced xanthine oxidase-derived superoxide production. These alterations demonstrate substantial dysregulation of arteriolar tone by the endothelium in HFD-induced obesity, which may contribute to disturbed tissue blood flow and development of increased peripheral resistance.
metabolic syndrome; high-fat diet; microvessel; endothelium; nitric oxide; superoxide; xanthine oxidase; allopurinol
This article has been cited by other articles:
|
|
 |
|
  M.-C. Aubin, C. Lajoie, R. Clement, H. Gosselin, A. Calderone, and L. P. Perrault Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 961 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Jebelovszki, C. Kiraly, N. Erdei, A. Feher, E. T. Pasztor, I. Rutkai, T. Forster, I. Edes, A. Koller, and Z. Bagi High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2558 - H2564. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
