Abstract 246: Role Of Cytochrome P450 4a2 In Mediating The Elevated Blood Pressure In A Rat Model Of Polycystic Ovary Syndrome
Women with polycystic ovary syndrome (PCOS) often have elevated blood pressure (BP). PCOS is characterized in part by increases in androgens, and androgens can increase cytochrome P450 (CYP) 4A isoforms and 20-HETE synthesis. We have found that CYP4A2 expression is increased in renal vasculature of hyperandrogenemic female rats, a model of PCOS. In the present study we tested the hypothesis that androgen increase would not cause elevated BP in CYP4A2-/- rats compared with wild type SS.Bn5 rats. CYP4A2-/- and SS.Bn5 rats (n=6-8/grp) were treated from 4 wks of age with dihydrotestosterone pellets (DHT 7.5 mg/90 d) or placebo pellets until 14 wks, and then telemetry transmitters were implanted. After 2 wks, mean arterial pressure (MAP) was measured for 10 days. DHT increased MAP and decreased HR in SS.Bn5 compared with placebo controls (placebo: 104±2 vs. DHT: 126±6 mmHg, p<0.001). In contrast, while placebo-treated CYP4A2-/- rats had higher MAP than WT, DHT did not increase BP in CYP4A2-/- rats (Placebo: 120±1 vs. DHT: 118±1 mmHg, p=NS). These data suggest that CYP4A2 may be necessary for DHT to increase BP in our model of PCOS. However, by what mechanism(s) CYP4A2-/- rats have higher MAP than SS.Bn5 WT remains to be determined. Supported by NIH R01HL66072, P01HL05971 and AHA 14POST18640015.
Author Disclosures: R.O. Maranon: None. C.N. Patil: None. C. Dalmasso: None. R. Roman: None. J.F. Reckelhoff: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2014 by American Heart Association, Inc.