Abolition of Hypertension-Induced End-Organ Damage by Anti-Androgen Treatment in Transgenic Rats Harboring the Mouse Ren-2 Gene
The possible involvement of androgen receptors in the development of hypertension and end-organ damage in transgenic rats harbouring the mouse Ren-2 renin gene [TGR(mREN2)27] was studied. Male TGR(mREN2)27 rats were treated with Flutamide (specific nonsteroidal competitive antagonist of the androgen receptor, 30 mg/kg/day) starting at 4 weeks of age. Blood pressure was monitored by telemetry until the establishment of hypertension (12 weeks of age). At the age of 12 weeks, urine was collected for albumin analysis (index of kidney damage). Then the rats were sacrificed and plasma angiotensinogen, renin and testosterone concentration, as well as kidney morphology were studied. Flutamide treatment produced a significant attenuation of the development of hypertension (systolic blood pressure: treated 189.7 ± 3.5 vs. control 222 ± 8 mm Hg). Heart hypertrophy was significantly reduced by the treatment (treated 0.35 ± 0.006 vs. control 0.43 ± 0.03 g/ 100 g b.w.). Urinary albumin excretion was blunted (treated 0.6 ± 0.1 vs. control 24.2 ± 7.7 mg/24 h) and no histological characteristics of end-organ damage were observed in the kidney after treatment. Flutamide treatment reduced plasma renin concentrations (treated 27.7 ± 2.7 vs. control 71.7 ± 28.5 ng/ ml), but not plasma angiotensinogen levels (treated 1.58 ± 0.1 vs. control 1.58 ± 0.1 μg/ ml). Testosterone levels increased 20 fold. Our results indicate that treatment with androgen receptor antagonist protects against end-organ damage and attenuate the hypertension in TGR(mREN2)27 rats.