HMOX1 and endothelial dysfunction: Since the side effects of chronic GTN therapy are mainly based on adverse regulation of mitochondrial function such as the inhibition of mitochondrial aldehyde dehydrogenase (ALDH-2) [23], increase in mitochondrial oxidative stress [23, 27], increase in cellular apoptosis [53], the induction of a mitochondrial antioxidant principle (HO-1) would be most effective to prevent GTN-induced tolerance and endothelial dysfunction.