Nitrate tolerance. A relevant clinical problem?

Tolerance to nitrates has been shown to develop rapidly during therapy in experimental animals and in man. Although tolerance to the haemodynamic effects was originally considered to be of no clinical significance, it has now been demonstrated to have a major effect on the management of patients with angina. The mechanism of tolerance is not clear, but the hypothesis that it is related to depletion of reduced sulfhydryl groups, with resultant decreased production of S-nitrosothiols and cyclic guanosine monophosphate, is not supported by our investigation. Although the mechanism of action is unknown, dosage strategies providing intermittent therapy with nitrates appear to be effective in preventing nitrate tolerance.