Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury.

Abstract

The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker with alpha-/beta-adrenoceptor blocking activities, on myocardial infarct size, apoptosis and necrosis in the rat after myocardial ischemia/reperfusion (45 min/120 min) were investigated. Ten minutes prior to left coronary artery occlusion, rats were treated with vehicle or labedipinedilol-A (0.25 or 0.5 mg/kg, i.v.). In the vehicle group, myocardial ischemia-reperfusion induced creatine kinase (CK) release and caused cardiomyocyte apoptosis, as evidenced by DNA ladder formation and terminal dUTP deoxynucleotidyltransferase nick end-labeling (TUNEL) staining. Treatment with labedipinedilol-A (0.25 or 0.5 mg/kg) reduced infarct size significantly compared to vehicle group (18.75+/-0.65% and 8.27+/-0.29% vs. 41.72+/-0.73%, P<0.01). Labedipinedilol-A also reduced the CK, CK-MB, lactate dehydrogenase (LDH) and troponin T levels in blood. In addition, labedipinedilol-A (0.5 mg/kg) significantly decreased TUNEL positive cells from 19.21+/-0.52% to 9.73+/-0.81% (P<0.01), which is consistent with absence of DNA ladders in the labedipinedilol-A group. Moreover, labedipinedilol-A pretreatment also decreased calcium content in ischemic-reperfused myocardial tissue. In conclusion, these results demonstrate that labedipindielol-A, through reduction of calcium overload and apoptosis, exerts anti-infarct effect during myocardial ischemia-reperfusion and would be useful clinically in the prevention of acute myocardial infarction.

• Authors: Jhy-Chong Liang, Hen-Rong Chen, Chaw-Chi Chiu, Shu-Fen Liou, Ing-Jun Chen, Jwu-Lai Yeh
• Journal: Life sciences (Life Sci) Vol. 79 Issue 13 Pg. 1248-56 (Aug 22 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16647091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anisoles
• Calcium Channel Blockers
• Cardiotonic Agents
• Dihydropyridines
• Troponin T
• labedipinedilol A
• DNA
• L-Lactate Dehydrogenase
• Creatine Kinase
• Calcium

Topics

• Anesthesia
• Animals
• Anisoles (pharmacology)
• Apoptosis (drug effects)
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Cardiotonic Agents
• Creatine Kinase (blood)
• DNA (biosynthesis, genetics)
• DNA Fragmentation
• Dihydropyridines (pharmacology)
• Hemodynamics (drug effects)
• In Situ Nick-End Labeling
• L-Lactate Dehydrogenase (blood)
• Male
• Myocardial Infarction (pathology)
• Myocardial Reperfusion Injury (pathology, prevention & control)
• Myocardium (metabolism)
• Myocytes, Cardiac (drug effects, pathology)
• Rats
• Rats, Wistar
• Troponin T (blood)