Experimental heart failure due to aortocaval shunt: role of kinins.

HECTOR NOLLY, ; BELISARIO FERNANDEZ, ; MARIELA NOLLY.

Congreso; American Hypertension Congress; 2002

P-275 EXPERIMENTAL HEART FAILURE DUE TO AORTOCAVAL SHUNT: ROLE OF KININS AND ANP Hector Nolly, Belisario Fernandez, Mariela Nolly. Hypertension Center, Mendoza and Faculty of Pharm and Biochem (UBA), Argentina. Angiotensin II (AII) has been implicated as a pathogenetic factor in hypertension (HT) and therefore blockade of the AT1 angiotensin receptor has been considered a therapeutic approach to treat hypertension. The AT1 receptor is responsible for the majority of the known effects of AII; however, the role of AT2 receptor is less well defined. We hypothesized that blockade of AT1 receptors increases AII levels, which in turn activates the AT2 receptor and through a kinin pathway induces cardioprotection. In addition, we investigate whether or not AII modulates the release of ANP in rats with aortocaval shunt. Fifty male Wistar rats (15030g) were used. To induce heart failure, we relied on the aortocaval shunt, an established model of moderate high-output heart failure. Cardiac mass and plasma ANP and cardiac kininogenase activity were estimated. Treatment with AT1 receptor antagonist Telmisartan significantly (p0.01) increased kininogenase activity (from 22014pg/mg to 158042) and plasma levels of ANP (from 485pg/ml to 32216). Treatment with Telmisartan significantly (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. Our results 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, perhaps acting via release of nitric oxide (NO) or by hyperpolarization caused by activation of potassium channels. Key Words: Kinins, Angiotensin, Angiotensin Receptor Blockers