Opening the calcium-activated potassium channel participates in the cardioprotective effect of puerarin.
The aim of the present study was to determine whether the effective cardioprotection conferred by puerarin against ischemia and reperfusion is mediated by the calcium-activated potassium channel. 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. Pretreatment with puerarin at 0.24 mmol/l for 5 min before ischemia increased myocardial formazan content and reduced LDH release during reperfusion. Administration of paxilline (1 micromol/l), an antagonist of the calcium-activated potassium channel, attenuated the protective effects of puerarin. In isolated ventricular myocytes, pretreatment with puerarin prevented simulated ischemia and reperfusion injury, hydrogen peroxide-induced cell death and the release of reactive oxygen species. Paxilline and chelerythrine (a protein kinase C inhibitor) both attenuated the effects of puerarin. These findings indicate that puerarin protects the myocardium against ischemia and reperfusion injury via opening the calcium-activated potassium channel and activating protein kinase C.
Gao
Qin
Q
Department of Physiology, Zhejiang University School of Medicine, 388 Yuhangtang Road, Hangzhou 310058, China.
Yang
Bo
B
Ye
Zhi-Guo
ZG
Wang
Jue
J
Bruce
Iain C
IC
Xia
Qiang
Q
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D000975:Antioxidants; D053119:Benzophenanthridines; D002316:Cardiotonic Agents; D007211:Indoles; D007529:Isoflavones; D024681:Potassium Channels, Calcium-Activated; C048220:paxilline; C016299:chelerythrine; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; C033607:puerarin