Author + information
- Received September 7, 2017
- Accepted September 19, 2017
- Published online October 30, 2017.
- Sanjay Divakaran, MD and
- Joseph Loscalzo, MD, PhD∗ ()
- ↵∗Address for correspondence:
Dr. Joseph Loscalzo, Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide–dependent and –independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin; thus, nitroglycerin is available in a number of preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch, as well as intravenous formulations. Organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major limitation of the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only 1 method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-h period. Nitric oxide’s important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator.
This work was supported in part by National Institutions of Health grants HL61795 and GM107618 (to Dr. Loscalzo). Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 7, 2017.
- Accepted September 19, 2017.
- 2017 American College of Cardiology Foundation
- Central Illustration
- Early History of the Use of Nitrates in Coronary Artery Disease
- NO in the Cardiovascular System
- Mechanism of Action of Nitrates
- Biotransformation of Organic Nitrates
- Hemodynamic Effects of Nitrates
- Nonhemodynamic Effects of Nitrates
- Clinical Uses of Nitrates
- Nitrate Tolerance
- Adverse Effects of Nitrates
- Novel Modulators of the NO-sGC-cGMP Pathway