Estudo do papel da angiotensina II na amplificação do edema de pata induzido por carragenina ou dextran em ratos / Study of the paper of the angiotensin II in the amplification of edema of induced leg for carrageenan or dextran in rats

AUTOR(ES)

Raquel Ferreira de Carvalho

DATA DE PUBLICAÇÃO

2005

RESUMO

Angiotensin II (Ang II) exerts its actions via AT1 and AT2 receptors. Recent studies have demonstrated that the renin-angiotensin system (RAS) participates in inflammation. The aim of this study was to evaluate the effect of Ang II on models of acute inflammation. Wistar rats were separated in the groups: saline (Sal), Ang II (1g), losartan (LOS, AT1 antagonist, 62.5g) and CGP42112A (AT2 agonist, 142.5g). Paw edema was induced by subplantar injection of carrageenan (Cg, 100g) or dextran (DXT, 100g) and was measured with a plethysmometer at 0, 1, 2, 3 and 4h. In the Sal and Ang II groups, paw tissue was taken to determine myeloperoxidase (MPO), IL-1 and TNF-α levels. Subcutaneus and mesenterium tissue were taken to evaluate mast cell degranulation through the toluidine blue staining. Sal and Ang II groups of DXT-induced paw edema were treated i.p. with mepyramine (MEP, anti-histamine, 10mg/kg) or metisergyde (MET, anti-serotonin, 1.5mg/kg) 1h prior to the injection of DXT. Ang II (0.5g/cavity, ip) was injected i.p. 1h before the i.p. injection of Cg to analyse the leukocytes migration to the peritoneal cavity. Ang II, LOS and CGP enhanced the Cg and DXT-induced paw edema and this enhancement was already significant at 1h. The administration of Ang II did not change the tissue content of MPO, TNF-α and IL-1 and did not induced or prevented neutrophil migration to peritoneal cavity, but induced significant enhancement of mast cell degranulation. MEP and MET reduced the Ang II-facilitated DXT-induced edema. Our results suggest that Ang II enhances the inflammatory response probably through the AT2 receptors since the AT1 antagonist, AT2 agonist and Ang II potentiated the paw edema. The data presented here also suggest that Ang II increases the vascular permeability through induction of mast cells degranulation, since there was early amplification of Cg paw edema and DXT vascular edema, and antagonists of serotonin and histamine significantly inhibited the increase in paw edema.

ASSUNTO(S)

anti-hipertensivos carrageenan angiotensin ii angiotensina ii carragenina inflammation sistema renina-angiotensina inibidores da enzima conversora da angiotensina captopril farmacologia inflamação

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