Androgen Receptor Blockade Differentially Regulates Blood Pressure in Growth-Restricted Versus Ovarian Deficient Rats.

Low birth weight is associated with a greater prevalence of hypertension in women by age 60; yet, the mechanisms involved are unknown. We previously reported that hypertension in female growth-restricted offspring that is associated with early reproductive senescence and a shift in the testosterone-to-estradiol ratio at 12 months of age is abolished by AR (androgen receptor) blockade in conjunction with downregulation of renal AT1aR (angiotensin type 1a receptor) mRNA expression. These data suggest androgen-mediated activation of the renin-angiotensin system contributes to the pathogenesis of hypertension that develops in female growth-restricted offspring with aging. Thus, this study tested the hypothesis that androgen-mediated increased blood pressure is specific to female growth-restricted offspring. Control and growth-restricted rats underwent sham or ovariectomy at 10 months of age. Vehicle or flutamide (8 mg/kg/day; subcutaneous), an AR antagonist, was administered at 11.5 months of age for 2 weeks followed by measurement of blood pressure. Loss of ovarian hormones was associated with a 10 mm Hg increase in blood pressure in control compared with intact counterparts accompanied by a 1.8-fold increase in renal AT1aR mRNA expression. Treatment with flutamide had no effect on blood pressure or renal AT1aR mRNA expression in ovariectomized controls. Although blood pressure was significantly decreased in flutamide-treated ovariectomized growth-restricted, flutamide had no effect on the increase in renal AT1aR mRNA expression. Therefore, these findings suggest the effect of AR blockade on blood pressure is specific to intact growth-restricted offspring and that mechanisms of postmenopausal hypertension may differ between normal and low birth weight women.