Evidence for a relationship between mitochondrial Complex I activity and mitochondrial aldehyde dehydrogenase during nitroglycerin tolerance: effects of mitochondrial antioxidants.

The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GIN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GIN tolerance (in rat and human vessels) produced a decrease in mitochondrial 02 consumption. Co-incubation with the mitochondria-targeted antioxidant mitoquinone (MQ 10(-6) mol/L) or with glutathione ester (GEE, 10(-4) mol/L) blocked GTN tolerance and the effects of GTN on mitochondrial respiration and aldehyde dehydrogenase 2 (ALDH-2) activity. Biotransformation of GTN depended on the mitochondria being functionally active, particularly mitochondrial Comp…