There is increasing evidence that attenuation of the beneficial effects of intravenous (i.v.) nitrate treatment may occur in various clinical settings, as is the case with other formulations such as transdermal nitroglycerin or sustained-release oral preparations, designed to produce steady-state plasma nitrate concentrations. Not all patients exhibit this phenomenon, but its incidence and predictive factor(s) are still unknown. The mechanisms of nitrate tolerance are controversial, but they involve changes at the smooth muscle cell level as well as neurohormonal activation