Postmenopausal Hypertension Is Blunted Following Chronic Flutamide Treatment in Intrauterine Growth Restricted Female Rat

Abstract

Intrauterine growth restriction (IUGR) programs the development of hypertension associated with increased adiposity and accelerated reproductive senescence by 12 months of age in female IUGR rats. At 12 months of age the estradiol (E) to testosterone (T) ratio is shifted with E levels remaining similar whereas T levels are increased in female IUGR relative to control. Postmenopausal women have a higher prevalence of hypertension associated with increased adiposity. In addition, blood pressure (BP) is increased in association with increased serum T in postmenopausal women. Thus, we tested the hypothesis that chronic blockade of the androgen receptor would attenuate hypertension in female IUGR rats at 12 months of age. Rats were treated with flutamide (8mg/kg/day), an androgen receptor antagonist, or vehicle subcutaneously for two weeks. BP was measured in conscious, chronically catheterized rats. T levels were measured via radioimmunoassay. BP was increased in IUGR relative to control at 12 months of age (Δ15 mmHg, P<0.05); T levels were also elevated in IUGR vs. control (45.33±3.48 vs. 37.56 ±1.72 pg/ml; P<0.05). Flutamide decreased BP in IUGR relative to untreated IUGR (Δ7 mmHg) with no impact in control (Δ0 mmHg). Flutamide did not alter fat mass. Thus, these data indicate that T contributes to the etiology of hypertension that develops with age following IUGR in the female rat. NIH: HL074927, HL51971, P20GM104357, AHA GRNT19900004