American Journal of Cardiovascular Drugs

, Volume 9, Issue 1, pp 7–15 | Cite as

Non-Hemodynamic Effects of Organic Nitrates and the Distinctive Characteristics of Pentaerithrityl Tetranitrate

  • Tommaso Gori
  • Andreas Daiber
Review Article


Organic nitrates are among the oldest and yet most commonly employed drugs in the long-term therapy of coronary artery disease and congestive heart failure. While they have long been used in clinical practice, our understanding of their mechanism of action and side effects remains incomplete. For instance, recent findings provide evidence of previously unanticipated, non-hemodynamic properties that include potentially beneficial mechanisms (such as the induction of a protective phenotype that mimics ischemic preconditioning), but also toxic effects (such as endothelial and autonomic dysfunction, rebound angina, tolerance). To date, the most commonly employed organic nitrates are isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin (glyceryl trinitrate). Another organic nitrate, pentaerithrityl tetranitrate (PETN), has long been employed in eastern European countries and is currently being reintroduced in Western countries. In light of their wide use, and of the (re)introduction of PETN in Western markets, the present review focuses on the novel effects of organic nitrates, describing their potential clinical implications and discussing differences among different compounds. We believe that these recent findings have important clinical implications. Since the side effects of organic nitrates such as nitroglycerin and isosorbides appear to be mediated by reactive oxygen species, care should be taken that drugs with antioxidant properties are co-administered. On the other hand, efforts should be made to clinically exploit the preconditioning effects of these drugs.


Autonomic Dysfunction Nicorandil PETN Isosorbide Dinitrate Organic Nitrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of this review. Andreas Daiber has received consultant and presenter honoraria from Actavis, has received a grant from Actavis, and is the recipient of a German Research Foundation grant (DFG, priority program [SFB] 553-C17). Tommaso Gori has received consultant honoraria from Actavis and 3M and is the recipient of a grant from the Italian Ministry of Research.


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Authors and Affiliations

  1. 1.Division of Cardiology, Department of MedicineMount Sinai and University Health Network Hospitals, University of TorontoTorontoCanada
  2. 2.Department of CardiologyUniversity of MainzMainzGermany
  3. 3.Department of CardiologyUniversity of MainzMainzGermany

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