Minoxidil attenuates ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes.
The effects of minoxidil (a mitochondrial K+(ATP) channel opener) on ischemia-induced necrosis and apoptosis were examined using a cardiomyocyte model of simulated ischemia, since mitochondrial K+(ATP) channel openers have been suggested to be involved in the mechanisms of cardioprotective action against ischemia/reperfusion injury. In the absence of minoxidil, simulated ischemia led to cellular release of creatine phosphokinase (CPK), morphologic degeneration, and beating cessation within 24 to 72 hours. Based on the Hoechst 33258 staining pattern, a significant number of cells placed in sealed flasks underwent apoptosis. Myocytes treated with 5 microM of minoxidil failed to alter the degree of ischemia-induced CPK loss for 48 to 72 hours. However, minoxidil treatment prevented the loss of beating function in many of the ischemic cells, and attenuated the decline in intracellular ATP content after a 48-hour ischemic incubation. The number of nuclear fragmentation was significantly reduced in minoxidil-treated cells after a 72-hour ischemic insult compared with untreated ischemic cells. This effect was blocked by the mitochondrial K+(ATP) channel antagonist 5-HD. The data suggest that minoxidil renders the cell resistant to ischemia-induced necrosis and apoptosis. The beneficial effects of minoxidil appear to be related to the opening of mitochondrial K+(ATP) channels.
Takatani
Tomoka
T
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Takahashi
Kyoko
K
Jin
Chengshi
C
Matsuda
Takahisa
T
Cheng
Xinyao
X
Ito
Takashi
T
Azuma
Junichi
J
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008914:Minoxidil / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D008914:Minoxidil