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(Hypertension. 2000;36:970.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Estrogen Replacement Reduces Age-Associated Remodeling in Rat Mesenteric Arteries

Yunlong Zhang; Ken G. Stewart; Sandra T. Davidge

From the Departments of Obstetrics/Gynecology and Physiology, Perinatal Research Centre, University of Alberta, Edmonton, Canada.

Correspondence to Sandra T. Davidge, PhD, 232 Heritage Medical Research Centre, Perinatal Research Centre, University of Alberta, Edmonton, Canada, T6G 2S2. E-mail sandra.davidge{at}ualberta.ca

Abstract—Estrogen replacement therapy significantly decreases the incidence of cardiovascular disease in postmenopausal women. In aging, there is an increase in vascular stiffness along with a decrease in matrix metalloproteinase (MMP) activity. Our hypothesis was that estrogen replacement would increase MMPs and therefore reduce the vascular stiffness that is associated with aging. Female Sprague-Dawley rats were implanted with a placebo or 17ß-estradiol–containing pellet (0.5 mg/pellet, 60-day release) at 10 months of age (n=6, each). Six young rats (3 months old) were also studied. After a 2-month exposure to the pellet, mesenteric arteries were studied on a pressurized arteriograph system. Distensibility and wall thickness were measured in response to stepwise increases in intraluminal pressure in Ca²⁺-free physiological saline solution buffer with papaverine (10^-4 mol/L). In response to increasing pressure, aged placebo rats exhibited a significant decrease in distensibility compared with young rats (P<0.05) that was accompanied by an increase in wall thickness (P<0.05). Conversely, estrogen replacement increased distensibility and decreased wall thickness in aged rats (old estrogen-replaced versus old placebo, P<0.05). Zymography data indicated that MMP-2 activity decreased in aging but was increased by estrogen replacement. In summary, estrogen replacement in aging female rats reduces age-associated vascular remodeling.

Key Words: estrogen • aging • vasculature • remodeling

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