The organic
nitrite, amyl of
nitrite, was initially used as a therapeutic agent in the treatment of
angina pectoris, but was replaced over a decade later by the organic
nitrate,
nitroglycerin (NTG), due to the ease of administration and longer duration of action. The administration of organic
nitrate esters, such as NTG, continues to be used in the treatment of
angina pectoris and
heart failure since the birth of modern pharmacology. Their clinical effectiveness is due to
vasodilator activity in large veins and arteries through an as yet unidentified method of delivering
nitric oxide (NO), or a NO-like compound. The major drawback is the development of tolerance with NTG, and the duration and route of administration with amyl of
nitrite. Although the
nitrites are no longer used in the treatment of
hypertension or
ischemic heart disease, the
nitrite anion has recently been discovered to possess novel
pharmacologic actions, such as modulating hypoxic vasodilation, and providing cytoprotection in
ischemia-reperfusion injury. Although the actions of these 2 similar chemical classes (
nitrites and organic
nitrates) have often been considered to be alike, we still do not understand their mechanism of action. Finally, the
nitrite anion, either from
sodium nitrite or an intermediate NTG form, may act as a storage form for NO and provide support for investigating the use of these agents in the treatment of ischemic cardiovascular states. We review what is presently known about the use of
nitrates and
nitrites including the historical, current, and potential uses of these agents, and their mechanisms of action.