Chronic Flutamide Treatment Alters Intrarenal Renin Angiotensin System Expression in Intrauterine Growth Restricted Female Rats
Designer JH, et al.
For many years, a relationship has been demonstrated between low birth weight and later development of cardiovascular and kidney disease in humans and in animal models. One model involves tying off uterine arteries late in rat pregnancy, effectively starving the pups. Female animals in this model develop hypertension as they age, as well as elevated testosterone levels and premature cessation of estrus cycling.
Post-cycling female IUGR rats underwent treatment for 2 weeks with vehicle or flutamide, an androgen receptor antagonist. This treatment blocked the development of hypertension in this model, as does renin-angiotensin blockade. The intrarenal renin-angiotensin system (RAS) was examined in these animals. Hypertensive females had elevated angiotensin receptors in the kidney. Flutamide treatment prevented this rise in receptors, suggesting that androgen-induced activation of the intrarenal RAS is the mechanism of hypertension in this model.
One criticism of this model is its severity; certainly further translational work is needed before we start treating postmenopausal women with flutamide for hypertension.