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The Androgen Receptor Contributes to Hypertension in Ovariectomized IUGR but Not in Ovariectomized Control Rats
Author(s) -
Davis Gwendolyn K.,
Newsome Ashley D.,
Alexander Barbara T.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.852.5
Subject(s) - medicine , endocrinology , ovariectomized rat , flutamide , blood pressure , testosterone (patch) , androgen , intrauterine growth restriction , androgen receptor , birth weight , estrogen , hormone , pregnancy , fetus , biology , prostate cancer , cancer , genetics
The prevalence of hypertension (HTN) is two‐fold higher in low birth weight (LBW) women at age 60 relative to normal birth weight ( NBW ) counterparts. Yet, the mechanisms that contribute to greater cardiovascular risk ( CVR ) in LBW women are unknown. Previous studies from our laboratory demonstrate that intrauterine growth restriction ( IUGR ) programs persistent estrus and a significant increase in circulating testosterone ( T ) and blood pressure ( BP ) in female Sprague Dawley ( SD ) IUGR rats at 12 months of age. Androgen receptor ( AR ) blockade abolishes HTN in female IUGR at 12 months of age indicating a role for the AR in the etiology of age‐dependent HTN in female IUGR. We previously reported that ovariectomy ( OVX ) at 10 weeks of age has no effect on BP or T levels in NBW ( control ) SD rats at 4 months of age. However, OVX at 10 months of age induces a significant increase in BP and T in SD controls compared to intact SD controls by 12 months of age. However, the importance of T in OVX‐induced HTN, a model of menopausal HTN, is not known. We tested the hypothesis that OVX‐induced HTN in female SD rats in later life is T dependent. Rats underwent sham ( intact ) or OVX at 10 months of age followed by vehicle or flutamide, an AR antagonist (8mg/kg/day, SC at 12 months of age for two weeks). Total fat and lean mass were measured via Echo MRI pre‐OVX and after treatment (Paired T‐test). BP was measured in conscious, chronically catheterized rats following treatment (2way ANOVA; Tukey's multiple comparison). BP was increased in vehicle OVX control relative to vehicle intact control (137±3 vs.129±3 mmHg, respectively). However, BP did not differ upon comparison of flutamide OVX control versus vehicle OVX control (140±7 mmHg) suggesting that OVX‐induced increase in BP in control rats does not involve a role for the AR. As observed previously, BP was not further elevated by OVX in IUGR. Furthermore, BP was decreased by 19 mmHg in flutamide intact IUGR relative to vehicle intact IUGR. Yet, BP was decreased by only 10 mmHg in flutamide OVX IUGR versus vehicle OVX IUGR suggesting that the importance of the AR in BP control may differ in ovarian intact IUGR versus ovarian deficient IUGR. OVX induced an increase in total fat mass, but attenuation of the OVX‐induced increase in total fat mass by flutamide was specific to IUGR (Table). Therefore, this study indicates that the AR contributes to enhanced CVR in female IUGR regardless of ovarian status, but not in OVX control SD rats. Support or Funding Information NIH: T32HL105324‐07, HL074927, HL51971, P20GM104357; AHA: GRNT19900004.Total Fat Mass (grams): Pre‐OVX Post‐TreatmentControl Vehicle 26±2 62±4 * Control Flutamide 34±7 60±10 * IUGR Vehicle 27±10 53±12 * IUGR Flutamide 22±3 35±8* P <0.05 vs Pre‐OVX.