Abstract P442: Estradiol Treatment Attenuates the Ovariectomy-induced Increase in Blood Pressure in the Middle Aged Dahl Salt Sensitive Rat as Long as Treatment is Initiated Immediately After Ovariectomy

Abstract

Introduction: Several studies have shown that ovariectomy increases blood pressure and that 17beta-estradiol ( E 2 ) treatment can attenuate this effect; however, the majority of these studies were conducted in young animals in which E 2 replacement was initiated soon after ovariectomy. Since most women who experience ovarian hormone loss are middle aged rather than young, this study investigated the effect of E 2 replacement in middle aged Dahl salt-sensitive ( DS ) rats. In addition, the time at which E 2 replacement was initiated was examined. Methods: DS rats were ovariectomized ( OVX ) at 4.5 months ( mo ) ( DS-OVX Y ) and 7mo ( DS-OVX O ). At 7mo, half of OVX DS rats in each group were treated with E 2 for 4 weeks ( DS-OVX Y +E 2 , DS-OVX O +E 2 ). Mean arterial pressure ( MAP ) was measured by telemetry in all treatment groups from 7-8mo. Body weights were measured throughout the experiment and plasma angiotensin II ( AngII ) was determined at time of sacrifice (8mo) by RAS fingerprint. Results: E 2 treatment at 7mo had no effect on MAP in the DS rats OVX at early age [MAP (mmHg) at 8mo: DS-OVX Y , 180±5.3 vs. DS-OVX Y +E 2 , 179±4.6, ns; n=4/group]. In contrast, one month of E 2 treatment prevented the ovariectomy-induced increase in MAP when OVX at late age [MAP (mmHg): DS-OVX O , 191±1.6 vs. DS-OVX O +E 2 , 177±2.9, p<0.0001 (Two-way ANOVA); n=4/group]. E 2 reduced the body weight ( BW ) by 26g in the DS-OVX Y group and prevented the ovariectomy-induced gain in BW by 39g in the DS-OVX O rats [BW(g): DS-OVX Y , 349±9 vs. DS-OVX Y +E 2 323±7, p<0.05; DS-OVX O , 334±7 vs. DS-OVX O +E 2 , 295±6, p<0.01; n=7-9/group]. E 2 also reduced plasma AngII in both the DS-OVX Y and DS-OVX O groups to similar extents [AngII (pg/ml): DS-OVX Y , 112±19 vs. DS-OVX Y +E 2 , 68.0±7.8, p<0.05; DS-OVX O , 113±11 vs. DS-OVX O +E 2 , 63.9±6.1, p<0.05; n=7-9/group]. Conclusions: These findings suggest E 2 replacement can attenuate the increase in MAP in middle age as a result of ovarian hormone loss. This study also supports the timing hypothesis that suggests E 2 treatment loses its protective blood pressure lowering effects if there is a significant time delay between ovarian hormone loss and E 2 replacement. These findings have implications for women who are ovarian hormone deficient and are considering E 2 replacement therapy.