Nitrate tolerance, oxidative stress, and mitochondrial function: another worrisome chapter on the effects of organic nitrates.

A shortcoming in the clinical use of organic nitrates is the development of tolerance. Recent data have suggested that the denitrification of organic nitrates is mediated by mitochondrial aldehyde dehydrogenase and that dysfunction of this enzyme is an important cause of tolerance. In this issue of the JCI, evidence in support of this hypothesis is presented in an in vivo model of nitrate tolerance (see the related article beginning on page 482).