Estrogen replacement reduces PGHS-2-dependent vasoconstriction in the aged rat.
The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunction. Models of aging have shown that this is due, in part, to increased prostaglandin H synthase (PGHS)-dependent vasoconstriction. We showed previously that inducible PGHS-2-dependent vasoconstriction is increased with aging. In the present study, we hypothesized that estrogen suppresses PGHS-2-dependent constriction in the aged rat. Isolated mesenteric arteries from placebo- or estrogen-treated, ovariectomized aged (24 mo) Fisher rats were assessed for endothelium-dependent relaxation in the absence or presence of PGHS inhibitors. PGHS inhibition (meclofenamate, 1 micromol/l) enhanced methacholine-induced relaxation only in the placebo group. Specific PGHS-2 inhibition (NS-398, 10 micromol/l) increased arterial relaxation to a greater extent than PGHS-1 inhibition (valeryl salicylate, 3 mmol/l). Estrogen prevented the PGHS-dependent constrictor effect but did not enhance nitric oxide-dependent relaxation in this model. PGHS-1 and endothelial nitric oxide synthase were not altered by estrogen, whereas PGHS-2 expression was decreased in the estrogen-replaced rats (P < 0.05). In summary, estrogen replacement improved vasodilation in aged rats by decreasing PGHS-dependent constriction.
Perinatal Research Centre and Departments of Obstetrics/Gynecology and Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Stephen J
SJ
Armstrong
Yunlong
Y
Zhang
Ken G
KG
Stewart
Sandra T
ST
Davidge
D000375:Aging / Q000502:physiology*; D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D010052:Ovariectomy; D010277:Parasympathomimetics / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013449:Sulfonamides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D010277:Parasympathomimetics; D013449:Sulfonamides; D016210:Methacholine Chloride; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009569:Nitric Oxide; D004958:Estradiol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases