A new transgenic rat model overexpressing the angiotensin II type 2 receptor provides evidence for inhibition of cell proliferation in the outer adrenal cortex

作者：Peters Barbara; Podlich Dirk; Ritter Michael; Mueller Anja; Wanka Heike; Maser Gluth Christiane; Seitz Claudia; de Boni Laura; Maier Elena; Gretz Norbert; Peters Joerg; Hoffmann Sigrid C^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2012, 302(9): E1044-E1054.

DOI：10.1152/ajpendo.00080.2011

• zona glomerulosa
• aldosterone production

Peters B, Podlich D, Ritter M, Muller A, Wanka H, Maser-Gluth C, Seitz C, de Boni L, Maier E, Gretz N, Peters J, Hoffmann SC. A new transgenic rat model overexpressing the angiotensin II type 2 receptor provides evidence for inhibition of cell proliferation in the outer adrenal cortex. Am J Physiol Endocrinol Metab 302: E1044-E1054, 2012. First published February 7, 2012; doi:10.1152/ajpendo.00080.2011.-This study aimed to elucidate the role of the AT(2) receptor (AT(2)R), which is expressed and upregulated in the adrenal zona glomerulosa (ZG) under conditions of increased aldosterone production. We developed a novel transgenic rat (TGR; TGRCXmAT(2)R) that overexpresses the AT(2)R in the adrenal gland, heart, kidney, brain, skeletal muscle, testes, lung, spleen, aorta, and vein. As a consequence the total angiotensin II (Ang II) binding sites increased 7.8-fold in the kidney, 25-fold in the heart, and twofold in the adrenals. The AT(2)R number amounted to 82-98% of total Ang II binding sites. In the ZG of TGRCXmAT(2)R, the AT(2)R density was elevated threefold relative to wild-type (WT) littermates, whereas AT(1)R density remained unchanged. TGRCXmAT(2)R rats were viable and exhibited normal reproduction, blood pressure, and kidney function. Notably, a slightly but significantly reduced body weight and a moderate increase in plasma urea were observed. With respect to adrenal function, 24-h urinary and plasma aldosterone concentrations were unaffected in TGRCXmAT(2)R at baseline. Three and 14 days of Ang II infusion (300 ng.min(-1).kg(-1)) increased plasma aldosterone levels in WT and in TGR. These changes were completely abolished by the AT(1)R blocker losartan. Of note, glomerulosa cell proliferation, as indicated by the number of Ki-67-positive glomerulosa cells, was stimulated by Ang II in TGR and WT rats; however, this increase was significantly attenuated in TGR overexpressing the AT(2)R. In conclusion, AT(2)R in the adrenal ZG inhibits Ang II-induced cell proliferation but has no obvious lasting effect on the regulation of the aldosterone production at the investigated stages.

• 出版日期2012-5