Estrogen replacement reduces age-associated remodeling in rat mesenteric arteries

Estrogen replacement therapy significantly decreases the incidence of cardi ovascular disease in postmenopausal women. In aging, there is an increase i n vascular stiffness along with a decrease in matrix metalloproteinase (MMP ) activity. Our hypothesis was that estrogen replacement would increase MMP s and therefore reduce the vascular stiffness that is associated with aging . Female Sprague-Dawley rats were implanted with a placebo or 17 beta -estr adiol-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-mo nth exposure to the pellet, mesenteric arteries were studied on a pressuriz ed arteriograph system. Distensibility and wall thickness were measured in response to stepwise increases in intraluminal pressure in Ca2+-free physio logical 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 i ncreased distensibility and decreased wall thickness in aged rats told estr ogen-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-associa ted vascular remodeling.