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.