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J Appl Physiol (May 28, 2004). doi:10.1152/japplphysiol.00242.2004
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Submitted on March 5, 2004
Accepted on May 21, 2004

AGE-RELATED ALTERATIONS IN NOS AND OXIDATIVE STRESS IN MESENTERIC ARTERIES FROM MALE AND FEMALE RATS

Jennifer C Sullivan1*, Elizabeth Dabbs Loomis1, Matthew Collins1, John D Imig2, Edward W Inscho3, and Jennifer S Pollock4

1 Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA
2 Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA; Department of Physiology, Medical College of Georgia, Augusta, GA, USA
3 Department of Physiology, Medical College of Georgia, Augusta, GA, USA
4 Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA; Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, USA

* To whom correspondence should be addressed. E-mail: jsullivan{at}mail.mcg.edu.

Epidemiological evidence suggests that advancing age affects the cardiovascular system of men and women differently. The purpose of this study was to determine if the effects of aging on NOS, oxidative stress, and vascular function are different in males and females. Mesenteric arteries from young (3 month) and old (24 month), male and female F344/BN rats were studied. Western blot analysis and NOS activity were performed on the homogenized mesenteric arterial bed separated into cytosolic and membrane-associated fractions. Plasma 8-isoprostane measurements assessed oxidative stress. Vascular reactivity was determined using a wire myograph in the absence and presence of a NOS inhibitor, N{omega}-nitro-L-arginine, to examine endothelial function, basal, and stimulated NO release. In additional arteries, reactivity was performed in the presence of PEG-SOD to assess the impact of superoxide on vascular function. Among females, aging was associated with a decline in membrane-associated NOS activity and membrane-associated NOS 3 protein expression. Advancing age in males was associated with increased cytosolic NOS 3 protein expression. Among both males and females, advancing age resulted in increased oxidative stress. Vascular function was maintained with age in arteries from both males and females, and there was no difference in either basal or stimulated NO release with age. Despite sex-specific effects of advancing age on the NOS system and increases in markers of oxidative stress, vascular function is maintained in mesenteric arteries from aged F344/BN rats. These data suggest that age-related alterations in the resistance vasculature are complex and likely involve multiple compensating vasoactive pathways.




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