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Estrogen replacement reduces PGHS-2-dependent vasoconstriction in the aged rat
Stephen J Armstrong1, Yunlong Zhang, Ken G Stewart
1Perinatal Research Centre and Departments of Obstetrics/Gynecology and Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
American Journal of Physiology. Heart and Circulatory Physiology
|August 16, 2002
Summary
Estrogen replacement therapy in aged rats reduced vascular dysfunction by decreasing prostaglandin H synthase (PGHS)-2-dependent vasoconstriction, improving blood vessel dilation.
Area of Science:
- Vascular Biology
- Endocrinology
- Aging Research
Background:
- Postmenopausal estrogen reduction is linked to increased vascular dysfunction.
- Aging exacerbates vascular dysfunction, partly via prostaglandin H synthase (PGHS)-dependent vasoconstriction.
- Previous work indicated increased PGHS-2-dependent vasoconstriction with aging.
Purpose of the Study:
- To investigate if estrogen suppresses PGHS-2-dependent constriction in aged rats.
- To determine the role of estrogen in modulating age-related vascular dysfunction.
Main Methods:
- Isolated mesenteric arteries from ovariectomized aged Fisher rats (placebo or estrogen-treated) were used.
- Endothelium-dependent relaxation was assessed with and without PGHS inhibitors (meclofenamate, NS-398, valeryl salicylate).
- PGHS-1, PGHS-2, and endothelial nitric oxide synthase (eNOS) expression and activity were analyzed.
Main Results:
- PGHS inhibition enhanced methacholine-induced relaxation in placebo but not estrogen-treated rats.
- Specific PGHS-2 inhibition yielded greater relaxation enhancement than PGHS-1 inhibition.
- Estrogen prevented PGHS-dependent constriction and decreased PGHS-2 expression, without altering PGHS-1 or eNOS.
Conclusions:
- Estrogen replacement therapy improves vasodilation in aged rats.
- This improvement is achieved by reducing PGHS-dependent constriction, specifically involving PGHS-2.
- Estrogen's beneficial effect on vascular function in aging is mediated, in part, by downregulating PGHS-2 expression.