Nitrate tolerance--mechanisms and prevention.

Nitrate tolerance is of significant clinical concern and every effort should be made to avoid this undesirable effect. The mechanism of tolerance is not clear but probably is multifactorial. Although ACE inhibitors, diuretics, and NAC have been tried as preventative measures, the only method proven to maintain nitrate effectiveness in patients is a nitrate-free interval. The results of further studies designed to determine the actual period of time that the patient is protected will be helpful. This may guide us in choosing the optimal nitrate therapy.