Endothelial dysfunction and infarct-size relate to impaired EDHF response in rat experimental chronic heart failure

被引:20
作者
Gschwend, S
Buikema, H
Henning, RH
Pinto, YM
de Zeeuw, D
van Gilst, WH
机构
[1] Univ Groningen, Dept Clin Pharmacol, NL-9713 AV Groningen, Netherlands
[2] Univ Groningen Hosp, Dept Cardiol, NL-9713 GZ Groningen, Netherlands
关键词
coronary ligation induced chronic heart failures infarct-size; endothelial dysfunction; nitric oxides; EDHF;
D O I
10.1016/S1388-9842(02)00248-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The rat coronary ligation model of chronic heart failure has been extensively used to investigate its pathophysiology including the role of endothelial dysfunction. Inconsistent results have been obtained concerning the role of endothelial dilative mediators nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Aims: Our aim was to investigate involvement of NO and EDHF in aortic endothelial dysfunction in this model and the influence of individual infarct sizes. Furthermore, we investigated whether it is justified to regard rats that failed to develop large infarct sizes as SHAM controls. Methods: We performed coronary ligations and SHAM operations and studied acetylcholine (ACh)-induced relaxations and underlying endothelial mediators in isolated aortic rings 12 weeks after infarction. By then, cardiac and hemodynamic parameters were deteriorated in animals with large myocardial infarctions (large-MI, 35 +/- 3%). but not those with small myocardial infarctions (small-MI, 5 +/- 2%). Results: Large-MI showed decreased ACh-induced relaxation compared to SHAM due to decreased contribution of EDHF which was inversely correlated with individual infarct-size. Interestingly. small-MI showed significantly increased ACh-induced relaxation compared to SHAM due to increased NO contribution. Conclusions: Our results suggest that impaired aortic endothelial dilatory function in large-MI is mainly due to an impaired EDHF response and strongly depends on individual infarct-size. In addition, endothelium-dependent relaxation of small-MI rats differed from SHAM, indicating that both groups may not be pooled to serve as controls. These results emphasize the importance of infarct-size and choice Of the control group, and may explain inconsistencies in previous studies. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:147 / 154
页数:8
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