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Title: Detrimental implication of B-1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice
Authors: Lagneux, C.
Bader, M.
Pesquero, J. B.
Demenge, P.
Ribuot, C.
Univ Grenoble 1
Max Delbruck Ctr Mol Med
Universidade Federal de São Paulo (UNIFESP)
Keywords: myocardial ischemia
isolated mouse heart
kinin B-1
gene knockout
Issue Date: 1-May-2002
Publisher: Elsevier B.V.
Citation: International Immunopharmacology. Amsterdam: Elsevier B.V., v. 2, n. 6, p. 815-822, 2002.
Abstract: 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.
ISSN: 1567-5769
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