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Molecular Medicine

, Volume 18, Issue 1, pp 1–9 | Cite as

Arrhythmogenic Effect of Sympathetic Histamine in Mouse Hearts Subjected to Acute Ischemia

  • Gonghao He
  • Jing Hu
  • Teng Li
  • Xue Ma
  • Jingru Meng
  • Min Jia
  • Jun Lu
  • Hiroshi Ohtsu
  • Zhong Chen
  • Xiaoxing Luo
Research Article

Abstract

The role of histamine as a newly recognized sympathetic neurotransmitter has been presented previously, and its postsynaptic effects greatly depended on the activities of sympathetic nerves. Cardiac sympathetic nerves become overactivated under acute myocardial ischemic conditions and release neurotransmitters in large amounts, inducing ventricular arrhythmia. Therefore, it is proposed that cardiac sympathetic histamine, in addition to norepinephrine, may have a significant arrhythmogenic effect. To test this hypothesis, we observed the release of cardiac sympathetic histamine and associated ventricular arrhythmogenesis that was induced by acute ischemia in isolated mouse hearts. Mast cell-deficient mice (MCDM) and histidine decarboxylase knockout (HDC−/−) mice were used to exclude the potential involvement of mast cells. Electrical field stimulation and acute ischemia-reperfusion evoked chemical sympathectomy-sensitive histamine release from the hearts of both MCDM and wild-type (WT) mice but not from HDC−/− mice. The release of histamine from the hearts of MCDM and WT mice was associated with the development of acute ischemia-induced ventricular tachycardia and ventricular fibrillation. The incidence and duration of induced ventricular arrhythmias were found to decrease in the presence of the selective histamine H2 receptor antagonist famotidine. Additionally, the released histamine facilitated the arrhythmogenic effect of simultaneously released norepinephrine. We conclude that, under acute ischemic conditions, cardiac sympathetic histamine released by overactive sympathetic nerve terminals plays a certain arrhythmogenic role via H2 receptors. These findings provided novel insight into the pathophysiological roles of sympathetic histamine, which may be a new therapeutic target for acute ischemia-induced arrhythmias.

Notes

Acknowledgments

The authors want to thank Xiang Gao and his associates of Model Animal Research Center of Nanjing University for their kind provision of Wads c-kit mutant mice (mast cell-deficient mice).

This work was supported by grants from the National Natural Science Foundation of China (30770669 and 30800310) and the National Science Foundation for Post-doctoral Scientists of China (20090451521).

Supplementary material

10020_2012_1801001_MOESM1_ESM.pdf (729 kb)
Arrhythmogenic Effect of Sympathetic Histamine in Mouse Hearts Subjected to Acute Ischemia

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Authors and Affiliations

  • Gonghao He
    • 1
    • 2
  • Jing Hu
    • 3
  • Teng Li
    • 3
  • Xue Ma
    • 1
  • Jingru Meng
    • 1
  • Min Jia
    • 1
  • Jun Lu
    • 1
  • Hiroshi Ohtsu
    • 4
  • Zhong Chen
    • 5
  • Xiaoxing Luo
    • 1
  1. 1.Department of Pharmacology, School of PharmacyThe Fourth Military Medical UniversityXi’anChina
  2. 2.Department of PharmacyKunming General Hospital of Chengdu Military RegionKunmingChina
  3. 3.Department of Histology and EmbryologyThe Fourth Military Medical UniversityXi’anChina
  4. 4.Department of Engineering, School of MedicineTohoku UniversitySendaiJapan
  5. 5.Department of Pharmacology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina

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