Vasodilation by nitroglycerin (NTG) and PETN: bioactivation to NO or a related species with subsequent activation of soluble guanylyl cyclase (sGC) and smooth muscle relaxation. Mechanisms underlying induction of vascular dysfunction by nitroglycerin and prevention of these adverse effects by activation of antioxidant, protective pathways by PETN: nitroglycerin induces mitochondrial and NADPH oxidase-dependent oxidative stress leading to uncoupling of eNOS and desensitization of sGC. PETN prevents these harmful events by induction of the antioxidant principle heme oxygenase and ferritin as well as others which are not shown here. Adopted from Gori et al., Arzneimitteltherapie 2008 [81].