Effect of aging, MnSOD deficiency, and genetic background on endothelial function: evidence for MnSOD haploinsufficiency.
OBJECTIVE
The goal of this study was to compare vascular function, superoxide levels, and MnSOD protein expression in young (4 to 7 months) and old (22 to 24 months) MnSOD+/+ and MnSOD-deficient (MnSOD+/-) mice.


RESULTS
Relaxation of aorta in vitro to the endothelium-dependent dilator acetylcholine (ACh) was similar in young MnSOD+/+ (n=9) and young MnSOD+/- (n=6) mice. This response was impaired in old MnSOD+/+ (n=8) mice and old MnSOD+/- mice (n=14), with dysfunction being greater in old MnSOD-deficient mice (eg, 100 micromol/L ACh produced 77+/-3% [mean+/-SE], 77+/-3%, 70+/-4%, and 57+/-4% relaxation in young MnSOD+/+, young MnSOD+/-, old MnSOD+/+, and old MnSOD+/- mice, respectively). The endothelial dysfunction was similar in mice on both C57BL/6 and CD-1 genetic backgrounds. In contrast to ACh, responses to the endothelium-independent dilator sodium nitroprusside were enhanced in old MnSOD+/+ and MnSOD+/- mice compared with both groups of young mice (P<0.05). Superoxide levels, as measured using lucigenin-enhanced chemiluminescence, were increased more than 2-fold in old MnSOD+/- mice compared with old MnSOD+/+ and young mice (P<0.05).


CONCLUSIONS
These data provide the first direct evidence that MnSOD haploinsufficiency results in increased vascular oxidative stress and endothelial dysfunction with aging.
Brown
Kathryn A
KA
Departments of Pharmacology, Cardiovascular Center, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
Didion
Sean P
SP
Andresen
Jon J
JJ
Faraci
Frank M
FM
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006239:Haplotypes / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D013482:Superoxide Dismutase; D000109:Acetylcholine