The effect of mebudipine on cardiac function and activity of the myocardial nitric oxide system in ischaemia-reperfusion injury in rats.

Abstract

OBJECTIVES:

Previous studies have suggested that failure of the synthesis of nitric oxide is involved in the pathophysiology of myocardial ischaemia-reperfusion injury. In this study, we investigated the effect of mebudipine, a new dihydropyridine calcium channel blocker, on cardiac function and activity of the myocardial nitric oxide system in ischaemia-reperfusion injury in isolated rat hearts.

METHODS:

Forty male Wistar rats (250-300 g) were divided into four groups (n = 10): sham, control, vehicle and drug groups. The animals were anesthetised with sodium pentobarbital (6 mg/kg intraperitoneal). The hearts were quickly removed, mounted on a Longendorff apparatus and perfused with Krebs-Henseleit solution under constant pressure at 37°C. After 20 min stabilisation period, the ischaemic groups received 30 min global ischaemia and 120 min reperfusion. For the drug and vehicle groups, before ischaemia the hearts were perfused with mebudipine (10(-3) µM) or ethanol-enriched solution (0.01%) for 25 min, respectively. Myocardial function, and creatine kinase, lactate dehydrogenase and total nitric oxide metabolite (nitrite and nitrate) levels were analysed.

RESULTS:

Cardiac functions had recovered significantly in the mebudipine group (p < 0.01). Furthermore, mebudipine remarkably reduced the levels of lactate dehydrogenase and creatine kinase in the coronary effluent and increased myocardial nitric oxide metabolite levels compared with the control group.

CONCLUSION:

Our results indicate that mebudipine reduced the intensity of myocardial ischaemia-reperfusion injury, and that activation of the myocardial nitric oxide system played an important role in this regard.

• Authors: R Ghyasi, M Mohammadi, R Badalzadeh, B Rashidi, G Sepehri
• Journal: Cardiovascular journal of Africa (Cardiovasc J Afr) 2011 Nov-Dec Vol. 22 Issue 6 Pg. 319-23 ISSN: 1680-0745 [Electronic] South Africa
• PMID: 22159320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Nitrates
• Nitrites
• mebudipine
• Nitric Oxide
• L-Lactate Dehydrogenase
• Creatine Kinase
• Nifedipine

Topics

• Animals
• Calcium Channel Blockers (pharmacology)
• Coronary Circulation (drug effects)
• Creatine Kinase (drug effects)
• Heart (drug effects)
• L-Lactate Dehydrogenase (drug effects)
• Male
• Myocardial Contraction (drug effects)
• Nifedipine (analogs & derivatives, pharmacology)
• Nitrates (metabolism)
• Nitric Oxide (metabolism)
• Nitrites (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (prevention & control)