Abstract |
Serotonin (5-HT) may play a role in exacerbating thrombosis and coronary spasm during myocardial ischemia, but its role in mediating myocardial damage directly is not clear. We determined the effect of the 5-HT2 receptor antagonists cinanserin (0.1-10 microM), ketanserin (0.3-10 microM), and LY 53857 (1-10 microM) on time to contracture, recovery of contractile function, and lactate dehydrogenase (LDH) release after 25-min global ischemia and 30-min reperfusion in isolated rat heart. All 5-HT2 antagonists significantly increased time to contracture in a concentration-dependent manner (EC25 = 1.6, 5.5, and 6.1 microM for cinanserin, ketanserin, and LY 53857, respectively). These compounds also significantly reduced LDH release and improved recovery of contractile function during reperfusion. 5-HT > or = 30 microM significantly reduced time to contracture, indicating a proischemic effect. The proischemic effect of 5-HT was abolished by ketanserin and cinanserin. Inhibition of 5-HT synthesis by parachlorophenylalanine resulted in significant cardioprotection, further indicating the involvement of 5-HT in the pathogenesis of ischemia in this model. Although cinanserin and ketanserin had alpha 1-adrenoceptor blocking effects, LY 53857 was devoid of this activity at concentrations exhibiting cardioprotection. Therefore, 5-HT may exacerbate ischemic injury in rat heart, and this exacerbation appears to be mediated specifically by 5-HT2 receptors.
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Authors | G J Grover, C A Sargent, S Dzwonczyk, D E Normandin, M J Antonaccio |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 22
Issue 4
Pg. 664-72
(Oct 1993)
ISSN: 0160-2446 [Print] United States |
PMID | 7505371
(Publication Type: Journal Article)
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Chemical References |
- Ergolines
- Receptors, Adrenergic, alpha
- Serotonin Antagonists
- Ketanserin
- L-Lactate Dehydrogenase
- Cinanserin
- LY 53857
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Topics |
- Animals
- Cinanserin
(pharmacology, therapeutic use)
- Disease Models, Animal
- Ergolines
(pharmacology)
- Heart
(drug effects, physiopathology)
- Hemodynamics
(drug effects)
- Ketanserin
(pharmacology, therapeutic use)
- L-Lactate Dehydrogenase
(metabolism)
- Male
- Muscle, Smooth, Vascular
(drug effects)
- Myocardial Contraction
(drug effects)
- Myocardial Ischemia
(drug therapy, physiopathology)
- Myocardial Reperfusion Injury
(drug therapy)
- Myocardium
(enzymology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Adrenergic, alpha
(drug effects, metabolism)
- Serotonin Antagonists
(pharmacology, therapeutic use)
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