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Nitroglycerin's Mechanism of Action to Improve Myocardial Oxygen Demand


The class of drugs called nitrates includes medications that are known to cause the formation and/or release of nitric oxide in the smooth muscle lining of blood vessels, thereby causing smooth muscle relaxation and vasodilatation.  Medications in this drug class include nitroglycerin, isosorbide dinitrate (ISDN, Isordil), and isosorbide mononitrate (which was previously marketed as Imdur).

Nitroglycerin's (as well as isosorbide dinitrate's) ability to improve myocardial oxygen demand has been shown to be from:

  • A reduction in mean blood pressure (on average is about 13 mm Hg)
  • Shorter ejection time (average 0.04 sec)
  • Reduction in preload that decreases end diastolic volumes and ventricular wall size
  • Redistribution of blood flow to the subendocardium of ischemic areas while maintaining flow in normal areas

The net improvement myocardial oxygen demand occurs despite an average increase in the pulse by 10 bpm.  When the National Heart and Lung Institute studied nitroglycerin in adults with stable angina undergoing exercise stress testing, nitroglycerin was shown to improve exercise capacity and delay the time of onset of ischemic electrocardiographic changes.  This study included both an evaluation of nitroglycerin and isosorbide dinitrate.

Anthony J. Busti, MD, PharmD, FNLA, FAHA
Editor:  Dylan Kellogg, MD
Last Reviewed:  August 2015

Landmark or Original Studies

  • Goldstein RE et al. Clinical and circulatory effects of isosorbide dinitrate. Comparison with nitroglycerin. Circulation 1971;43(5):629-40. PubMed
    Level of Evidence 1b
    Study Design Prospective, Randomized, Placebo Controlled, Single-Center Study
    Sample Size N = 23
    Population Adults with stable angina for at least 6 months who underwent exercise stress testing and randomly received either nitroglycerin, isosorbide dinitrate (ISDN), or placebo in doses enough to produce a 10 mm Hg decrease in the mean arterial blood pressure.
    • Ten minutes after ISDN 21 of 23 patients exercised longer (average 2.7 min, P < 0.001) vs placebo.
    • There was a lower mean blood pressure (average 13 mm Hg, P < 0.001), higher heart rate (average 10 beats/min, P < 0.001), and shorter ejection time (average 0.04 second, P < 0.001) after ISDN. Similar changes were seen after nitroglycerin.
    Conclusions ISDN resembles nitroglycerin in effects on changing circulatory function during exercise as well as improved duration exercise and overall exercise capacity.
    Comments This is one of the primary references cited by the NSTEMI Guidelines to support the use of nitroglycerin in the early or acute management NSTEMI even though the patients in this study had stable angina and were undergoing exercise stress testing.
    Location National Hearth and Lung Institute, Bethesda, MD

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MESH Terms or Keywords

  • NTG Use in Acute Coronary Syndrome, Nitroglycerin NTG Mechanism to Improve Myocardial Oxygenation, Nitroglycerin Oxygen Demand