Tolerance can occur with long-term nitrate drugs, i.e., the hemodynamic and anti-ischemic effects of nitrate drugs may be weakened, and their tolerance not only makes the drug effect weaken or even disappear, but also causes the hemodynamic response of peripheral vasculature and coronary arteries to weaken or disappear. Continuous use of nitrates is prone to tolerance, and it is related to the dose used and the duration of continuous use. Cross-tolerance exists between different nitrates, but tolerance appears and disappears quickly. In the case of long-term use of anti-cardiac drugs or long-acting nitrate preparations, long-term use is still effective if there is a nitrate-free interval of 10 to 12 hours per day. Combination with other vasodilators can also reduce the tolerance of nitrates. Some studies suggest that nitrate tolerance is related to excessive sulfhydryl depletion in the body, so some angiotensin-converting enzyme inhibitors containing sulfhydryl groups, such as Kepone, can be used in combination.