title: Aging and estrogen alter endothelial reactivity to reactive oxygen species in coronary arterioles.
abstract: Endothelium-dependent, nitric oxide (NO)-mediated vasodilation can be impaired by reactive oxygen species (ROS), and this deleterious effect of ROS on NO availability may increase with aging. Endothelial function declines rapidly after menopause, possibly because of loss of circulating estrogen and its antioxidant effects. The purpose of the current study was to determine the role of O(2)(-) and H(2)O(2) in regulating flow-induced dilation in coronary arterioles of young (6-mo) and aged (24-mo) intact, ovariectomized (OVX), or OVX + estrogen-treated (OVE) female Fischer 344 rats. Both aging and OVX reduced flow-induced NO production, whereas flow-induced H(2)O(2) production was not altered by age or estrogen status. Flow-induced vasodilation was evaluated before and after treatment with the superoxide dismutase (SOD) mimetic Tempol (100 μM) or the H(2)O(2) scavenger catalase (100 U/ml). Removal of H(2)O(2) with catalase reduced flow-induced dilation in all groups, whereas Tempol diminished vasodilation in intact and OVE, but not OVX, rats. Immunoblot analysis revealed elevated nitrotyrosine with aging and OVX. In young rats, OVX reduced SOD protein while OVE increased SOD in aged rats; catalase protein did not differ in any group. Collectively, these studies suggest that O(2)(-) and H(2)O(2) are critical components of flow-induced vasodilation in coronary arterioles from female rats; however, a chronic deficiency of O(2)(-) buffering by SOD contributes to impaired flow-induced dilation with aging and loss of estrogen. Furthermore, these data indicate that estrogen replacement restores O(2)(-) homeostasis and flow-induced dilation of coronary arterioles, even at an advanced age.
authors: Dept. of Physiology and Functional Genomics, Univ. of Florida, 1600 SW Archer Rd., P.O. Box 100274, Gainesville, FL 32610, USA.
authors: Lori S
authors: LS
authors: Kang
authors: Bei
authors: B
authors: Chen
authors: Rafael A
authors: RA
authors: Reyes
authors: Amanda J
authors: AJ
authors: Leblanc
authors: Bunyen
authors: B
authors: Teng
authors: S Jamal
authors: SJ
authors: Mustafa
authors: Judy M
authors: JM
authors: Muller-Delp
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D004967:Estrogens; D017382:Reactive Oxygen Species; D013113:Spin Labels; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; C001803:tempol