This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Takano, S. Articles by Kimura, J. Search for Related Content PubMed Articles by Takano, S. Articles by Kimura, J. Social Bookmarking                         What's this?

Dual Roles of 5-Hydroxytryptamine in Ischemia-Reperfusion Injury in Isolated Rat Hearts

Yuji Hoshino, MD

Libing Li, MD

Isao Matsuoka, PhD

Tomoyuki Ono, PhD

Junko Kimura, MD

Department of Pharnacology, School of Medicine, Fukushima Medical University, Fukushima, Japan

Background: 5-Hydroxytryptamine (5-HT) has been shown to be involved in exacerbating cardiac ischemia-reperfusion injury; however, the role of 5-HT in the injury has yet to be established. This study demonstrates that 5-HT has dual roles in ischemia-reperfusion injury.

Methods and Results: The role of 5-HT in cardiac ischemia-reperfusion injury was examined in isolated rat hearts perfused with oxygenated Krebs-Henseleit solution. A 30-minute global ischemia and 30-minute reperfusion exacerbated functional cardiac parameters such as left ventricular end-diastolic pressure, coronary flow, heart rate, and total lactate dehydrogenase release. The 5-HT₂A receptor antagonist sarpogrelate (0.3-1.0 µM) improved cardiac function during ischemia-reperfusion. High-performance liquid chromatography analysis revealed an elevation in the level of 5-HT in the coronary effluent immediately after ischemia, suggesting that 5-HT is released from the ischemic heart and that sarpogrelate protects the heart from ischemia-reperfusion injury by blocking 5-HT₂A receptors. However, 5-HT (0.3-1.0,µM) applied exogenously unexpectedly improved the cardiac mechanical parameters during ischemia-reperfusion, increased coronary flow, and increased the level of NO in the effluent, which was inhibited by L-N^G-nitro-arginine methyl ester, a NO synthase blocker.

Conclusions: Present results suggest dual roles of 5-HT in ischemia-reperfusion injury. During ischemia, 5HT is released endogenously, constricts coronary smooth muscles via 5-HT2A receptors, and aggravates cardiac function. In contrast, 5-HT applied exogenously affects predominantly non-5HT₂A receptors on the endothelium and induces coronary vasodilatation via endothelial NO production, which is protective against ischemia-reperfusion injury.

Key Words: 5-Hydroxytryptamine • ischemia and reperfusion • 5-HT2A receptors • exogenous • 5-HT • NO

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 9, No. 1, 43-50 (2004)
DOI: 10.1177/107424840400900i107


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. Bianchi, O. Kunduzova, E. Masini, C. Cambon, D. Bani, L. Raimondi, M.-H. Seguelas, S. Nistri, W. Colucci, N. Leducq, et al. Oxidative Stress by Monoamine Oxidase Mediates Receptor-Independent Cardiomyocyte Apoptosis by Serotonin and Postischemic Myocardial Injury Circulation, November 22, 2005; 112(21): 3297 - 3305. [Abstract] [Full Text] [PDF]