GW24-e0440 Diazoxide inhibits the opening of MPTP after hypoxia/reoxygenation injury in myocardial cells through alleviation of calcium overload and ATP deficiency

Objectives Diazoxide, a mitoK ATP channel opener can inhibit the opening of mitochondrial permeability transition pore (MPTP) in myocardial cells after hypoxia/reoxygenation injury. The mechanisms are not clear. We hypothesised that the protective effects of Diazoxide might be related to the modulation of the intracellular calcium and ATP homeostasis. Methods Cultured neonatal rats cardiomyocytes were subjected to 1 hour hypoxia followed by 2 hours reoxygenation (H/R) and divided randomly into the following groups: (1) control: no H/R and no interventions; (2) H/R; (3) Diaz: 1000 μmol/L diazoxide were given; (4) 5-HD + Diaz: 1000 μmol/L 5-hydroxydecanoic acid (5-HD, a mitoK ATP channel inhibitor) were given prior to diazoxide; (5) Atr + Diaz: 100 μmol/L atractyloside (Atr, a MPTP opener) were given before diazoxide; (6) Atr: 100 μmol/L atractyloside were given alone; (7) NaOH: 0.01 mmol/L NaOH (a solvent for all those drugs) were given alone. All the drugs were given at the 15 th min after reoxygenation. Results After intervention with Diazixide during reoxgenation, the opening of MPTP was decreased significantly (0.96 ± 0.02 in Diaz vs 0.72 ± 0.04 in H/R, p Conclusions The cardioprotective effect of mitoK ATP channel opener is induced by inhibiting the opening of MPTP via alleviation of calcium overload and ATP deficiency so as to prevent mitochondrial dysfunction and cell apoptosis during early reoxygenation.