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BIBTEX RIS

Characterization of a new angiotensin antagonist selective for angiotensin-(1–7): Evidence that the actions of angiotensin-(1–7) are mediated by specific angiotensin receptors

1994; Elsevier BV; Volume: 35; Issue: 4 Linguagem: Inglês

10.1016/0361-9230(94)90104-x

1873-2747

Robson A.S. Santos, Maria José Campagnole‐Santos, Nilo C.V. Baracho, Marco Antônio Peliky Fontes, Luciana C.S. Silva, Liomar A. A. Neves, Djenane Ramalho de Oliveira, Sordaini Maria Caligiorne, Adriana R. Rodrigues, Carlos Gropen, Wânia S. CARVALHO, Ana Cristina Simões e Silva, Mahesh C. Khosla,

Neuropeptides and Animal Physiology

In this study we describe a new angiotensin antagonist [Asp1-Arg2-Val3-Tyr4-Ile5-His6-D-Ala7, (A-779)] selective for the heptapeptide angiotensin-(1–7) [Ang-(1–7)]. A-779 blocked the antidiuretic effect of Ang-(1–7) in water-loaded rats and the changes in blood pressure produced by Ang-(1–7) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostral ventrolateral medulla, the pressor effect produced by Ang-(1–7) microinjection was completely blocked by A-779 but not by AT1 or AT2 receptor antagonists (DUP 753 and CGP 42112A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for 125I-Ang II binding to adrenocortical membranes at up to a 1 μM concentration. Low affinity binding was also observed in adrenomedullary membranes with an IC50 greater than 10 μM. Our results show that A-779 is a potent and selective antagonist for Ang-(1–7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-(1–7).