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Int J Exp Pathol ; 94(1): 17-24, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23176371

RESUMO

The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar-Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I(2) -receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I(1) -receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (K(ATP) ) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I(2) -receptor, which is expressed more highly in SHRs.


Assuntos
Agmatina/farmacologia , Anti-Hipertensivos/farmacologia , Aorta Torácica/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Receptores de Imidazolinas/agonistas , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta Torácica/metabolismo , Aorta Torácica/fisiopatologia , Benzofuranos/farmacologia , Western Blotting , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Imidazóis/farmacologia , Receptores de Imidazolinas/metabolismo , Canais KATP/antagonistas & inibidores , Canais KATP/metabolismo , Masculino , Bloqueadores dos Canais de Potássio/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Regulação para Cima
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