Detrimental implication of B-1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice

Detrimental implication of B-1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice

Autor Lagneux, C. Google Scholar
Bader, M. Google Scholar
Pesquero, J. B. Google Scholar
Demenge, P. Google Scholar
Ribuot, C. Google Scholar
Instituição Univ Grenoble 1
Max Delbruck Ctr Mol Med
Universidade Federal de São Paulo (UNIFESP)
Resumo Objective: the aim of this study was to evaluate the contribution of kinin B-1 receptors in myocardial ischemia using both pharmacological blockade and gene knockout mice. Material and methods: Hearts (n=6-8 per group) from wild type or homozygous B-1 receptor gene knockout mice were isolated and perfused using the Langendorff technique. After a 30-min stabilisation period, the left coronary artery was occluded for 30 min followed by 60 min of reperfusion. in two separate groups of wild type hearts, B-1 and B-2 receptors were blocked with 3 nM of (des-Arg(9), Leu(8))-bradykinin and 10 nM of Hoe 140, respectively, (started 15 min before ischemia and stopped before the reperfusion). Results: Infarct size to risk zone (I/R) ratio was significantly reduced in hearts of knockout mice (11.3 +/- 2.1%) compared to those of wild type mice (25.7 +/- 1.7%). Furthermore, in wild type mice, I/R was significantly reduced in hearts perfused with the B-1 receptor antagonist (12.8 +/- 2.4%) but not in hearts perfused with the B-2 receptor antagonist (36.3 4.4%) compared to untreated hearts. Finally, a RTPCR technique showed an activation of kinin B-1 receptor gene transcription, in wild type hearts, subjected to the ischemia-reperfusion sequence. Conclusion: This study demonstrates that B-1 receptors are induced during myocardial ischemia where they could play a detrimental role in mice. (C) 2002 Published by Elsevier Science B.V.
Palavra-chave myocardial ischemia
isolated mouse heart
kinin B-1
receptors
gene knockout
Idioma Inglês
Data de publicação 2002-05-01
Publicado em International Immunopharmacology. Amsterdam: Elsevier B.V., v. 2, n. 6, p. 815-822, 2002.
ISSN 1567-5769 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 815-822
Fonte http://dx.doi.org/10.1016/S1567-5769(02)00022-X
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000176444700010
Endereço permanente http://repositorio.unifesp.br/handle/11600/26857

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