| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Vascular Biology Center and Departments of Physiology and Pharmacology, Medical College of Georgia, Augusta, Georgia 30912; and 2St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia
Submitted 22 March 2004 ; accepted in final form 15 July 2004
Previously, using an animal model of syndrome X, the obese Zucker rat (OZR), we documented impaired endothelium-dependent vasodilation. The aim of this study was to determine whether reduced expression or altered posttranslational regulation of endothelial nitric oxide synthase (eNOS) underlies the vascular dysfunction in OZR rats. There was no significant difference in the relative abundance of eNOS in hearts, aortas, or skeletal muscle between lean Zucker rats (LZR) and OZR regardless of age. There was no difference in eNOS mRNA levels, as determined by real-time PCR, between LZR and OZR. The inability of insulin resistance to modulate eNOS expression was also documented in two additional in vivo models, the ob/ob mouse and the fructose-fed rat, and in vitro via adenoviral expression of protein tyrosine phosphatase 1B in endothelial cells. We next investigated whether changes in the acute posttranslational regulation of eNOS occurs with insulin resistance. Phosphorylation of eNOS at S632 (human S633) and T494 was not different between LZR and OZR; however, phosphorylation of S1176 was significantly enhanced in OZR. Phosphorylation of S1176 was not different in the ob/ob mouse or in fructose-fed rats. The association of heat shock protein 90 with eNOS, a key regulatory step controlling nitric oxide and aberrant O2– production, was not different between OZR and LZR. Taken together, these results suggest that changes in eNOS expression or posttranslation regulation do not underlie the vascular dysfunction seen with insulin resistance and that other mechanisms, such as altered localization, reduced availability of cofactors, substrates, and the elevated production of O2–, may be responsible.
syndrome X; Zucker; obesity
This article has been cited by other articles:
|
|
 |
|
  C. Blouet, F. Mariotti, V. Mathe, D. Tome, and J.-F. Huneau Nitric Oxide Bioavailability and Not Production Is First Altered During the Onset of Insulin Resistance in Sucrose-Fed Rats Experimental Biology and Medicine, December 1, 2007; 232(11): 1458 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Focardi, G. M. Dick, A. Picchi, C. Zhang, and W. M. Chilian Restoration of coronary endothelial function in obese Zucker rats by a low-carbohydrate diet Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2093 - H2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. K. Johnson, R. A. Johnson, W. Durante, K. E. Jackson, B. K. Stevenson, and K. J. Peyton Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R601 - R608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Frisbee Reduced nitric oxide bioavailability contributes to skeletal muscle microvessel rarefaction in the metabolic syndrome Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R307 - R316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Molnar, S. Yu, N. Mzhavia, C. Pau, I. Chereshnev, and H. M. Dansky Diabetes Induces Endothelial Dysfunction but Does Not Increase Neointimal Formation in High-Fat Diet Fed C57BL/6J Mice Circ. Res., June 10, 2005; 96(11): 1178 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Phillips, F. A. Sylvester, and J. C. Frisbee Oxidant stress and constrictor reactivity impair cerebral artery dilation in obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R522 - R530. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
