[Tolerance of nitrate derivatives: pharmacologic and clinical aspects]

The authors emphasize the importance of the phenomenon of vascular tolerance to organic nitrates. Its mechanisms remain controversial but there are compelling evidences supporting the role of the availability of sulfhydryl groups in vascular smooth muscle cells. Nitrate tolerance can be avoided or minimized with dosing strategies that use intermittent administration of nitrates, using the smallest effective dose and providing a nitrate-free interval. The preventive role of N-acetyl-cysteine is briefly discussed as well as the absence of cross-tolerance observed with sydnonimines.