Dual roles of 5-hydroxytryptamine in ischemia-reperfusion injury in isolated rat hearts.
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.


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-HT(2A) receptor antagonist sarpogrelate (0.3-1.0 microM) 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-HT(2A) receptors. However, 5-HT (0.3-1.0 microM) 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-HT(2A) receptors, and aggravates cardiac function. In contrast, 5-HT applied exogenously affects predominantly non-5HT(2A) receptors on the endothelium and induces coronary vasodilatation via endothelial NO production, which is protective against ischemia-reperfusion injury.
Takano
Shizuko
S
Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan. s-takano@fmu.ac.jp
Hoshino
Yuji
Y
Li
Libing
L
Matsuoka
Isao
I
Ono
Tomoyuki
T
Kimura
Junko
J
D000818:Animals; D004727:Endothelium; D016166:Free Radical Scavengers / Q000032:analysis; D006321:Heart / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology*; D014664:Vasodilation
D016166:Free Radical Scavengers; D009569:Nitric Oxide; D012701:Serotonin