Angiotensin II receptors blockade: role of bradykinin.

H. NOLLY; A. NOLLY; M. ROMERO; MARIELA NOLLY

Congreso; American Hypertension Congress; 2000

ANGIOTENSIN II RECEPTOR BLOCKADE: ROLE OF BRADYKININ H. Nolly*, A. Nolly, M. Romero and M. Nolly. Lab. of Experimental Hypertension, School of Medicine, Mendoza, Argentina Angiotensin II (AII) is a potent vasopressor peptide and has been implicated as a pathogenetic factor in hypertension. Inhibition of AII has therefore, been considered a therapeutic approach to treat hypertension. AII has two major receptor isoform, AT1 and AT2. The AT1 is responsible for the majority of the known effects of AII, much less is known about the AT2 receptor stimulation. The aim of this study was to evaluate whether Telmisartan and Irbesartan two selective antagonist of AT1 receptors could play a protective role for the heart and kidneys. In one experimental model of hypertension (AII-induced hypertension with osmotic pumps) the AT1 receptor antagonist was not only an effective antihypertensive agent (162 6 5 mmHg in HT vs. 110 6 4 in HT-treated, p , 0.01) but also reduced proteinuria (78 6 9 mg/d in HT vs. 26 6 5 in HT-treated, p , 0.01). In angiotensin-induced hypertension as well as in one experimental model of chronic heart failure due to aorto-caval shunt, both AII antagonist significantly protect against cardiac hypertrophy (1.82 6 12 g in shunt vs. 1.28 6 7 g in shunt-treated, p , 0.01). This cardioprotective effect was abolished by the kinin B2 receptor antagonist, icatibant. This would favour the contention that the blockade of the AT1-mediated effects of angiotensin explains the antihypertensive action, leaving the AT2 receptor unopposed. We conclude that the organ-protective actions of the AT1 receptor antagonist may involve AT2 and bradykinin B2-receptors mediated effects, perhaps acting via release of NO or hyperpolarization caused by activation of potassium channels. Key Words: Angiotensin; receptors; cardiovascular protection; hypertension Supported by FONCYT: 05-0000-01541