Abolition of End-Organ Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats

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Abstract
We aimed at studying the role of androgens in the development of cardiovascular pathology in hypertensive female rats. Female TGR(mREN2)27 rats harboring the mouse Ren-2 renin gene were treated with Flutamide (specific antagonist of the androgen receptor, 30 mg/kg per day) starting at 4 weeks of age. Flutamide treatment significantly attenuated the development of hypertension in female rats (systolic blood pressure: treated, 134.5±5.4 versus control, 165.4±3.8 mm Hg). Heart hypertrophy was significantly reduced by the treatment (treated, 0.37±0.008 versus control, 0.45±0.01 g/100 g body wt). Urinary albumin excretion was blunted (treated, 0.4±0.1 versus control, 23.1±7.5 mg/24 hours), collagen III mRNA was significantly decreased, and no histological characteristics of end-organ damage were observed in the kidney after treatment. Flutamide treatment significantly reduced plasma renin concentrations and rat renin mRNA in kidney but not plasma angiotensinogen levels. Plasma levels of estrogens, testosterone, and luteinizing hormone were not altered. These results demonstrate that the androgen receptor antagonist Flutamide protects against hypertension and end-organ damage not only in male but also in female TGR(mREN2)27 rats.