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 developm ent of hypertension and zona glomerulosa (ZG) hyperfunction in the transgen ic rat strain TGR[mREN2]27 (TGR) has been investigated. Male heterozygous T GR were given per os for 4 weeks the Ang-II AT1 receptor antagonist irbesar tan (50 mg/kg day) or the mixed ETA/ETB receptor antagonist bosentan (100 m g/kg day), A group of TGR received a placebo gavage. Irbesartan lowered blo od pressure (BP), while bosentan was ineffective. Conversely, both antagoni sts decreased plasma aldosterone concentration, the volume of ZG and its pa renchymal cells, and in vitro aldosterone secretion by capsule-ZG preparati ons. 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) hypera ldosteronism does not contribute significantly to the development of hypert ension in TGR. (C) 2000 Elsevier Science Inc. All rights reserved.