Bioactivation, mitochondrial effects and mechanisms of vasodilatation induced by aminoethyl nitrate (AEN) and other organic nitrates in the study of Schuhmacher et al. (2009). Both the highly potent nitroglycerin (GTN) and the less potent triethanolamine trinitrate (TEAN) are bioactivated by mitochondrial aldehyde dehydrogenase (mtALDH) and produce considerable amounts of mitochondrial reactive oxygen and nitrogen species (ROS/RNS, most probably peroxynitrite). In contrast, the trinitrate metabolite of pentaerithrityl tetranitrate, PETriN, also bioactivated by the mtALDH, did not induce mitochondrial oxidative stress. None of the mononitrates was bioactivated by mtALDH. Nevertheless, AEN was almost as potent as GTN and much more potent than methyl-3-nitrooxypropanoate (NPME), which showed significantly higher vasodilator potency than isopropyl nitrate (IPM). None of the mononitrates increased ROS/RNS levels in isolated mitochondria. Whether AEN, NPME and IPM undergo mitochondrial metabolism remains to be established. AEN-induced vasodilatation was attenuated by the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) and the inhibitor of soluble guanylate cyclase, NS2028. The lack of effect of miconazol on AEN-induced relaxation makes it unlikely that AEN was metabolized by cytochrome P450 enzymes. Attenuation of AEN-induced relaxation by allopurinol indicated that xanthine oxidase (XO) may be involved in bioactivation of AEN.