Role of at2 receptor in the protective effect of telmisartan in cardiac tissue

HECTOR L NOLLY, ; PABLO A OSSO, ; MARIELA B NOLLY.

Congreso; American Hypertension Congress; 2004

P-339 ROLE OF AT2 RECEPTOR IN THE PROTECTIVE EFFECT OF TELMISARTAN IN CARDIAC TISSUE Hector L Nolly, Pablo A Osso, Mariela B Nolly. Hypertension, Hypertension Center, Mendoza, Mendoza, Argentina; Hypertension, Faculty of Biochemistry (UJAM), Mendoza, Mendoza, Argentina.Blockade of the AT1 angiotensin receptor is considered an excellent therapeutic approach to treat hypertension (HT). The AT1 receptor is responsible for the majority of the known effects of AII; however, the role of AT2 receptor is less well defined. It was hypothesized that blockade of AT1 receptor increases AII levels, which in turn activates the AT2 receptor and through a kinin pathway induces cardioprotection. Ninety male Wistar rats (130 30g) were used to induce an experimental model of hypertension (aortic banding) and one experimental model of chronic heart failure (aorto-caval shunt) respectively. Aortocaval shunt is an established model of moderate high-output heart failure. Cardiac mass and plasma ANP and cardiac kininogenase activity were estimated In aortic-banding HT rats, treatment with the AT1 receptor antagonist Telmisartan not only reduce blood pressure (162 5mmHg in HT vs. 110 4 in HT-treated, p0.01) and cardiac mass (p0.01) but also significantly increased kininogenase activity (from 228 16 pg Bk/mg/h to 560 42; p0.01). In addition, in rats with aortocaval shunt Telmisartan significantly (p0.01) increased kininogenase activity (from 220 14 pg/mg to 1580 42) and plasma levels of ANP (from 48 5 pg/ml to 322 16). Treatment with Telmisartan (p0.01) prevent cardiac mass increase and this effect was blunted by the kinin B2- receptor antagonist icatibant and by the AT2 receptor antagonist PD123319. The present data suggest that the AII-mediated stimulation of the AT2 receptor alone and/or through the release of kinins may be an important component of the cardioprotective effect of Telmisartan. Key Words: Hypertension, Angiotensin-Receptor Blockers, Kinins