Many estrogen-replacement studies use ovariectomized animals as controls. H
owever, ovariectomy greatly increases body weight and can enhance the perip
heral synthesis of estrogen. Tamoxifen is commonly used as an antiestrogen,
but it may elicit mixed agonist or antagonist actions. The aim of our stud
y was to compare vascular function in mesenteric arteries among groups of r
ats with low estradiol levels. The groups (n = 5, each) of Sprague-Dawley r
ats were cycling (diestrus), ovariectomized (OVX), OVX + tamoxifen (OVX-T),
OVX + 4-hydroxyandrostene- 3,17-dione, an aromatase inhibitor (OVX-A) to p
revent peripheral synthesis of estrogen, and control-fed OVX to prevent exc
ess weight gain. Body weight was significantly elevated in only the non-con
trol-fed OVX group. Estrogen levels were significantly greater in the cycli
ng rats compared with the other groups, whereas uterine weights were signif
icantly reduced in only the OVX-A and control-fed OVX groups. Methacholine
relaxation was blunted only in the OVX-A and control-fed OVX groups, sugges
ting a possible estrogenic influence in the non-control-fed OVX and OVX-T g
roups. These data indicate the potential for confounding factors to decreas
e the efficacy of OVX controls.