Estrogen upregulates renal angiotensin II AT2receptors

Abstract

AT2 receptors may act in opposition to and in balance with AT1 receptors, their stimulation having beneficial effects. We found renal AT2receptor expression in female mice higher than in male mice. We asked the question of whether such expression might be estrogen dependent. In male, female, ovariectomized, and estrogen-treated ovariectomized mice, we studied renal AT1 and AT2 receptors by immunocytochemistry and autoradiography, AT2 receptor mRNA by RT-PCR, and cAMP, cGMP, and PGE2 by RIA. AT1receptors predominated. AT2 receptors were present in glomeruli, medullary rays, and inner medulla, and in female kidney capsule. AT1 and AT2 receptors colocalized in glomeruli. Female mice expressed fewer glomerular AT1receptors. Ovariectomy decreased AT1 receptors in medullary rays and capsular AT2 receptors. Estrogen administration normalized AT1 receptors in medullary rays and increased AT2 receptors predominantly in capsule and inner medulla, and also in glomeruli, medullary rays, and inner stripe of outer medulla. In medullas of estrogen-treated ovariectomized mice there was higher AT2 receptor mRNA, decreased cGMP, and increased PGE2 content. We propose that the protective effects of estrogen may be partially mediated through enhancement of AT2 receptor stimulation.