Abstract P043: Estradiol Treatment Duration Significantly Impacts Renal Health in Midlife Ovariectomized Female Long Evans Rats
Current clinical recommendations are that hormone therapy for the treatment of menopausal symptoms be limited to a few years. Our lab previously reported that both transient (40 days) and sustained (80 days) estradiol (E2) treatment initiated immediately after midlife ovariectomy (OVX) in Long Evans rats similarly attenuated OVX-induced increases in blood pressure (BP). This study indicated that the benefits of E2 could be maintained long after treatment cessation. Therefore, the goal of the current study was to determine whether E2 duration similarly protected against renal damage. We hypothesized that both transient and sustained E2 treatment exert positive effects on renal health in midlife OVX Long Evans female rats. Female retired breeders underwent OVX at 11 months of age and received an implant of E2 or vehicle (veh). After 40 days, implants were replaced comprising the following groups: veh>veh (n=9), E2>E2 (n=7), E2>veh (n=10). Animals were placed in metabolic cages at both the 40 and 80 day treatment time points to measure proteinuria, urinary peptides, and creatinine excretion. At the end of the 80 day treatment tissue weights were obtained. Interestingly, kidney hypertrophy was significantly increased in the E2>E2 when analyzed as raw wet weight (veh: 1.0 ± 0.05 g; E2>veh: 0.95 ± 0.02; E2>E2: 1.2 ± 0.04; P<0.0001), or normalized to body weight (veh: 2.5 ± 0.1 mg/gBW; E2>veh: 2.5 ± 0.03; E2>E2: 2.9 ± 0.11; P<0.005). Creatinine excretion was not different between groups (veh: 7.0 ± 0.6 mg/day; E2>veh: 6.4 ± 0.4; E2>E2: 7.6 ± 0.7; P=0.29). However, there was a significant increase in proteinuria measured by the Bradford assay in the E2>E2 group (veh: 2.0 ± 0.8 mg/mgCr; E2>veh: 0.9 ± 0.3; E2>E2: 6.8 ± 2.6; P<0.05). The E2>E2 group also had a significantly lower percentage of urinary peptides (veh: 96 ± 0.8%; E2>veh: 97 ± 0.7%; E2>E2: 79 ± 8.1%; P<0.05), indicating impaired renal function. These results indicate that in midlife OVX Long Evans rats, sustained E2 lowered BP but exerted detrimental effects on kidney function. In contrast, transient E2 treatment lowered BP without renal impairment. Overall, our results indicate that the period of exposure to estradiol may be important for renal health in aging postmenopausal women.
Author Disclosures: M.A. Zimmerman: None. E.H. Trimmer: None. J.M. Daniel: None. S.H. Lindsey: None.
- © 2015 by American Heart Association, Inc.