Effects of N-n-butyl haloperidol iodide on rat myocardial ischemia and reperfusion injury and L-type calcium current.

Abstract

AIM:

To study the effects of N-n-butyl haloperidol iodide (F2) on rat heart ischemia/reperfusion (I/R) injury and L-type calcium current (ICa) in rat ventricular myocytes.

METHODS:

Rat heart I/R injury was induced by occluding the left anterior descending coronary artery for 30 min and restoring perfusion for 30 min. F2 (1, 2, and 4 mg/kg) were i.v. injected before ischemia. Plasma creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), glutamic-oxaloacetic transaminase (GOT), malondialdehyde (MDA) concentrations, and superoxide dismutase (SOD) activity were measured. The pathologic changes of I/R myocardium were assessed by the transmission electron microscopy. Single rat ventricular myocyte was obtained by enzymatic dissociation method. The currents were recorded with the whole-cell configuration of the patch-clamp technique.

RESULTS:

F2 reduced the release of CK, CK-MB, LDH, HBDH and GOT, preserved the activity of SOD, and decreased the MDA contents dose-dependently. For morphology, F2 mollified the pathologic changes of myocardium induced by I/R injury. F2 1 micromol/L decreased ICa from (1775+/-360) pA to (464+/-129) pA (n=8, P<0.01) and shifted the current-voltage of ICa upward, without affecting the voltage-depend-ent properties of ICa.

CONCLUSION:

F2 played a protective role against rat heart I/R injury in a dose-dependent manner, and inhibited ICa in rat ventricular myocytes. The cardioprotective and vasodilatory mechanisms of F2 may be related to its inhibitory effect on L-type calcium channel.

• Authors: Zhan-Qin Huang, Gang-Gang Shi, Jin-Hong Zheng, Bing Liu
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 24 Issue 8 Pg. 757-63 (Aug 2003) ISSN: 1671-4083 [Print] United States
• PMID: 12904274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels, L-Type
• Cardiotonic Agents
• N-n-butyl haloperidol iodide
• Haloperidol

Topics

• Animals
• Calcium Channels, L-Type (drug effects, metabolism)
• Cardiotonic Agents (chemical synthesis, therapeutic use)
• Haloperidol (analogs & derivatives, chemical synthesis, pharmacology, therapeutic use)
• Microscopy, Electron
• Myocardial Ischemia (complications)
• Myocardial Reperfusion Injury (etiology, prevention & control)
• Myocardium (ultrastructure)
• Random Allocation
• Rats
• Rats, Sprague-Dawley