Functional evidence for an active role of B-type natriuretic peptide in cardiac remodelling and pro-arrhythmogenicity

被引:32
作者
Thireau, Jerome [1 ]
Karam, Sarah [1 ]
Fauconnier, Jeremy [1 ]
Roberge, Stephanie [1 ]
Cassan, Cecile [1 ]
Cazorla, Olivier [1 ]
Aimond, Franck [1 ]
Lacampagne, Alain [1 ]
Babuty, Dominique [2 ]
Richard, Sylvain [1 ]
机构
[1] Univ Montpellier 2, Univ Montpellier 1, CHU Arnaud de Villeneuve, INSERM U1046, F-34295 Montpellier, France
[2] Hop Trousseau, Tours, France
关键词
Natriuretic peptide; Heart failure; Arrhythmia; Calcium; Remodelling; HEART-RATE-VARIABILITY; SARCOPLASMIC-RETICULUM; FAILING HEARTS; BETA-BLOCKERS; FAILURE; CALCIUM; S100A1; NESIRITIDE; THERAPY; RELEASE;
D O I
10.1093/cvr/cvs167
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims During heart failure (HF), the left ventricle (LV) releases B-type natriuretic peptide (BNP), possibly contributing to adverse cardiovascular events including ventricular arrhythmias (VAs) and LV remodelling. We investigated the cardiac effects of chronic BNP elevation in healthy mice and compared the results with a model of HF after myocardial infarction (PMI mice). Methods and results Healthy mice were exposed to circulating BNP levels (BNP-Sham) similar to those measured in PMI mice. Telemetric surface electrocardiograms showed that in contrast with fibrotic PMI mice, electrical conduction was not affected in BNP-Sham mice. VAs were observed in both BNP-Sham and PMI but not in Sham mice. Analysis of heart rate variability indicated that chronic BNP infusion increased cardiac sympathetic tone. At the cellular level, BNP reduced Ca2+ transients and impaired Ca2+ reuptake in the sarcoplasmic reticulum, in line with blunted SR Ca2+ ATPase 2a and S100A1 expression. BNP increased Ca2+ spark frequency, reflecting Ca2+ leak through ryanodine receptors, elevated diastolic Ca2+, and promoted spontaneous Ca2+ waves. Similar effects were observed in PMI mice. Most of these effects were reduced in BNP-Sham and PMI mice by the selective beta 1-adrenergic blocker metoprolol. Conclusion Elevated BNP levels, by inducing sympathetic overdrive and altering Ca2+ handling, promote adverse cardiac remodelling and VAs, which could account in part for the progression of HF after MI. The early use of beta-blockers to prevent the deleterious effects of chronic BNP exposure may be beneficial in HF.
引用
收藏
页码:59 / 68
页数:10
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