From the Guidelines
Nitroglycerin works primarily as a vasodilator by reducing myocardial oxygen demand and enhancing myocardial oxygen delivery through its effects on both peripheral and coronary vascular systems.
Mechanism of Action
The mechanism of action of nitroglycerin involves the dilation of capacitance vessels, which increases venous pooling and decreases myocardial preload, thereby reducing ventricular wall tension and myocardial oxygen demand (MVO2) 1.
- It also has modest effects on the arterial circulation, decreasing systolic wall stress (afterload) and contributing to further reductions in MVO2.
- Additionally, nitroglycerin dilates normal and atherosclerotic epicardial coronary arteries and smaller arteries, promoting the dilation of large coronary arteries, as well as collateral flow and redistribution of coronary blood flow to ischemic regions.
- The medication also inhibits platelet aggregation, although the clinical significance of this action is not well defined 1.
Clinical Applications
Nitroglycerin is commonly used to treat angina and other cardiovascular conditions, and it comes in various formulations, including sublingual tablets, spray, transdermal patches, and intravenous forms 1.
- The suitable dose and duration of effect vary depending on the formulation and route of administration, with common doses ranging from 0.3 to 0.6 mg for sublingual tablets and 5 to 200 mcg per min for intravenous administration.
- However, it is essential to consider the potential contraindications, such as the use of phosphodiesterase inhibitors like sildenafil, tadalafil, or vardenafil, which can lead to profound hypotension and other adverse effects when combined with nitroglycerin 1.
From the FDA Drug Label
Mechanism of Action: Nitroglycerin forms free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation The mechanism of action (MOA) of nitroglycerin is through the formation of free radical nitric oxide (NO), which activates guanylate cyclase, leading to an increase in cyclic GMP in smooth muscle and other tissues, resulting in vasodilatation 2.
- The key steps in the MOA are:
- Formation of nitric oxide (NO)
- Activation of guanylate cyclase
- Increase in cyclic GMP
- Vasodilatation due to dephosphorylation of myosin light chains
From the Research
Mechanism of Action of Nitroglycerin
The mechanism of action (MOA) of nitroglycerin (glyceryl trinitrate) involves the relaxation of vascular smooth muscle cells, leading to vasodilation. The key points of this mechanism are:
- Nitroglycerin stimulates the enzyme guanylate cyclase in smooth muscle cells, producing cyclic guanosine-3',5'-monophosphate (cGMP) 3
- The increase in cGMP levels leads to a decrease in free calcium concentration in the cytosol, resulting in relaxation of vascular smooth muscle cells 3
- Nitroglycerin activates nitric oxide (NO)-cyclic guanosine-3',-5'-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation 4
- The anti-angina effects of nitrates are mostly due to peripheral venous dilatation, leading to reduction in preload and left ventricular wall stress, and to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure 4
Role of Nitric Oxide
Nitric oxide (NO) plays a crucial role in the MOA of nitroglycerin. The key points are:
- Nitroglycerin generates NO through enzyme-mediated reactions in vascular smooth muscle cells 5
- The metabolic conversion of nitroglycerin to NO is essential for its pharmacologic action, viz. relaxation 5
- Inhibitors of glutathione-S-transferases (GSTs) can affect NO generation from nitroglycerin, but the exact mechanism is still unclear 5
Tolerance Development
Repeated use of nitroglycerin can lead to tolerance, which is characterized by a loss of its vasodilatory efficacy. The key points are: