Effects of irbesartan and bosentan on the blood pressure and adrenal zona glomerulosa function in heterozygous transgenic TGR[mREN2]27 rats

The role of angiotensin-II (Ang-II) and endothelin-1 (ET-1) in the development of hypertension and zona glomerulosa (ZG) hyperfunction in the transgenic rat strain TGRmREN2]27 (TGR) has been investigated. Male heterozygous TGR were given per os for 4 weeks the Ang-II ATI receptor antagonist irbesartan (50 mg/kg x day) or the mixed ETA/ETB receptor antagonist bosentan (100 mg/kg x day). A group of TGR received a placebo gavage. Irbesartan lowered blood pressure (BP), while bosentan was ineffective. Conversely, both antagonists decreased plasma aldosterone concentration, the volume of ZG and its parenchymal cells, and in vitro aldosterone secretion by capsule-ZG preparations. Collectively, our results allow us to conclude that (i) only Ang-II is involved in the genesis of hypertension in TGR, while both endogenous Ang-II and ET-1 play a role in the genesis of ZG hyperfunction; and (ii) hyperaldosteronism does not contribute significantly to the development of hypertension in TGR.