Effects of estrogens and selective estrogen receptor modulators (SERMs) on vascular reactivity in the perfused mesenteric vascular bed Running head: Mesenteric vascular responses to estrogens and SERMs

Estrogens, and SERMs such as raloxifene (RAL) and tamoxifen (TAM), acutely relax arteries, but the long term effects of estrogens and SERMs on vascular reactivity in the mesenteric vasculature have not been well-defined. In this study, we used an isolated perfused mesenteric vascular bed technique to investigate the effect of chronic treatment of estrogens and SERMs on vascular reactivity of the mesenteric bed. Ovariectomized female Sprague Dawley rats were treated by gavage with vehicle (CTL, 2-hydroxypropyl-β-cyclodextrin), ethinyl estradiol (EE), estradiol benzoate (EB), equilin (EQ), TAM, or RAL for 3 weeks. EQ and TAM increased vasoconstriction in response to all three vasoconstrictors tested (KCl, NE, and 5-HT). EE increased vasoconstriction in response to KCl and 5-HT, whereas responses to EB and RAL were less consistent. Only EQ (134 ± 4 mmHg) and TAM (104 ± 4) changed mean arterial blood pressure compared to control (117 ± 4). These data demonstrate that 3 week gavage treatment with estrogens and SERMs affects vascular reactivity in the mesenteric vascular bed. However, the three formulations of estrogen did not produce equivalent effects, and the effects of the SERMs were different from those of the estrogens. Key terms: equilin, ethinyl estradiol, estradiol benzoate, tamoxifen, raloxifene Page 2 of 31