Abstract 443: Androgen-Sensitive Hypertension in Adult mRen2.Lewis Rats

Abstract

The mRen2.Lewis (mRen2) rat is an angiotensin II-dependent model of hypertension that displays marked sex differences in systolic blood pressure (SBP). Gonadectomy (GDX) of young female mRen2 rats significantly increases SBP; however, the role of androgens has not been assessed. In addition, the impact of GDX in adult rats with well-established hypertension is not known. Therefore, the current study assessed the impact of adult gonadectomy (GDX; 17 weeks of age) on established hypertension and associated end organ damage in mRen2 rats. Baseline SBP at 16 weeks of age was not different between male groups (214 ± 13 mmHg, n=5 vs. 224 ± 3 mmHg, n=3, P>0.05) but was significantly lower in females (143 ± 9 mmHg, n=3, P<0.01). GDX significantly lowered SBP in males after one week (159 ± 13 mmHg, P<0.001), and SBP remained lower until 25 weeks of age (169 ± 9 mmHg, P<0.05). The lower SBP in GDX males was associated with a significant reduction in kidney weight (3.1 ± 0.02 vs. 2.9 ± 0.06 mg/g body weight, P<0.05), heart weight (4.1 ± 0.10 vs. 3.4 ± 0.12 mg/g body weight, P<0.01), and proteinuria (53 ± 7 vs. 20 ± mg/kg/day, P<0.01) at 25 weeks of age. Proteinuria in GDX males remained significantly higher in comparison to GDX females (3.9 ± 0.6 mg/kg/day, P<0.01). In summary, GDX of adult male but not female mRen2 rats had a significant and rapid impact on blood pressure and was associated with a reduction in end organ damage. When combined with our previous work in the female mRen2 rat, we conclude that estrogens may play a critical role in the development of hypertension in younger females, while androgens apparently contribute to the maintenance of blood pressure in adult males. This animal model may be relevant to discern the complex relationships between sex hormones, hypertension, and tissue damage. Future studies will establish the molecular pathways by which each of these steroid hormones interacts with the renin-angiotensin system to modulate blood pressure in the mRen2 strain.