Atractyloside and 5-hydroxydecanoate block the protective effect of puerarin in isolated rat heart.

Abstract

The aim of the present study was to determine whether the clinically effective cardioprotection conferred by puerarin (Pue) against ischemia and reperfusion is mediated by mitochondrial transmembrane pores and/or channels. Hearts isolated from male Sprague-Dawley rats were perfused on a Langendorff apparatus and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The production of formazan, which provides an index of myocardial viability, was measured by absorbance at 550 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was determined. In this model, Pue (0.0024-2.4 mmol/l) had a dose-dependent, negatively inotropic effect. Pretreatment with Pue at 0.24 mmol/l for 5 min before ischemia increased myocardial formazan content, reduced LDH release, improved recovery of left ventricular end-diastolic pressure and rate-pressure product (left ventricular developed pressure multiplied by heart rate) during reperfusion. Administration of atractyloside (20 micromol/l), an opener of the mitochondrial permeability transition pore, for the first 20 min of reperfusion, and 5-hydroxydecanoate (100 micromol/l), the mitochondrial-specific ATP-sensitive potassium channel blocker, for 20 min before ischemia, attenuated the protective effects of Pue. In mitochondria isolated from hearts pretreated with 0.24 mmol/l Pue for 5 min, a significant inhibition of Ca(2+)-induced swelling was observed, and this inhibition was attenuated by 5-hydroxydecanoate. In isolated ventricular myocytes, pretreatment with Pue prevented ischemia-induced cell death and depolarization of the mitochondrial membrane, and atractyloside and 5-hydroxydecanoate attenuated the effects of Pue. These findings indicate that puerarin protects the myocardium against ischemia and reperfusion injury via inhibiting mitochondrial permeability transition pore opening and activating the mitochondrial ATP-sensitive potassium channel.

• Authors: Qin Gao, Hong-Yang Pan, Shuang Qiu, Yuan Lu, Iain C Bruce, Jian-Hong Luo, Qiang Xia
• Journal: Life sciences (Life Sci) Vol. 79 Issue 3 Pg. 217-24 (Jun 13 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16458326 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Decanoic Acids
• Hydroxy Acids
• Isoflavones
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Potassium Channel Blockers
• Potassium Channels
• mitochondrial K(ATP) channel
• Atractyloside
• 5-hydroxydecanoic acid
• puerarin

Topics

• Animals
• Atractyloside (pharmacology)
• Cardiotonic Agents (antagonists & inhibitors, pharmacology)
• Decanoic Acids (pharmacology)
• Heart (drug effects)
• Hydroxy Acids (pharmacology)
• In Vitro Techniques
• Isoflavones (antagonists & inhibitors, pharmacology)
• Male
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Permeability Transition Pore
• Myocardial Reperfusion Injury (metabolism, prevention & control)
• Myocardium (metabolism)
• Potassium Channel Blockers (pharmacology)
• Potassium Channels (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley