Androgens and Angiotensin #expbio

Apr 06 2016 Published by under EB2016

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.

Mr. T, aka Testosterone

Mr. T, aka Testosterone

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.

2 responses so far

  • Newbie says:

    Other caveat for all rodent models of steroid action is that rat and mouse adrenals do not synthesize DHEA. Although a small source of T, the adrenals in older-men/post-menopausal women,are important sites of steroid precursor synthesis in humans.

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