Nitrates and Nitrites in the Treatment of Ischemic Cardiac Disease

Abstract

The organic nitrite, amyl of nitrite, was initially used as a therapeutic agent in the treatment of angina pectoris in 1867, 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 during the birth of modern pharmacology. The 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 to vascular smooth muscle cells. The major drawback with NTG administration is the rapid development of tolerance; and with amyl of nitrite, the duration and route of administration. Although amyl of nitrite are no longer used in the treatments 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 two similar chemical classes (nitrites and organic nitrates) have often been considered to be alike, we still do not understand their mechanism of action. However, the recent discovery that the nitrite anion, derived from either sodium nitrite or an intermediate NTG form, may act as a storage form for NO and provides 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 nitrites and nitrates, the potential uses of these agents, and their mechanisms of action.

Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy

“…The mechanism of action in these drugs is traditionally believed to result from their arterial vasodilation and venodilation effects and improvement of collateral blood flow, resulting in decreased myocardial oxygen consumption and reduced cardiac workload (98). Recently, it has been recognized that these drugs also have intrinsic antiplatelet and antithrombotic effects, demonstrated both in vitro and in vivo, which adds further rationale for their use in atherothrombotic diseases.…”

Intravascular Residence Time Determination for the Cyanide Antidote Dimethyl Trisulfide in Rat by Using Liquid-Liquid Extraction Coupled with High Performance Liquid Chromatography

“…Earlier studies were focusing on the methemoglobin forming effect of sodium nitrite as a scavenger type antidote [4]. Recent studies are focusing on the nitric oxide donor role within the mitochondria as the primary antidotal mechanism of sodium nitrite [5]. Cyanokit has the active ingredient of hydroxocobalamin, which can scavenge CN to form the stable cyanocobalamin complex [6].…”

Modulated nitric oxide delivery in three-dimensional biomaterials for vascular functionality

“…[32] Amyl nitrite is used as a therapeutic agent for angina initially, and superseded a decade later by organic nitrates such as GTN, due to the ease of administration and longer duration of action. [33] Organic nitrates have been investigated extensively for numerous CVDs ranging from the heart failure to anal fissures.…”