Nitrate tolerance does not increase production of peroxynitrite in the heart

T. Csont, C. Csonka, Annamária Ónody, A. Görbe, L. Dux, Richard Schulz, Gary F. Baxter, P. Ferdinándy

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Clinical studies have suggested that long-term nitrate treatment does not improve and may even worsen cardiovascular mortality, and the possible role of nitrate tolerance has been suspected. Nitrate tolerance has been recently shown to increase vascular superoxide and peroxynitrite production leading to vascular dysfunction. Nevertheless, nitrates exert direct cardiac effects independent from their vascular actions. Therefore, we investigated whether in vivo nitroglycerin treatment leading to vascular nitrate tolerance increases cardiac formation of nitric oxide (NO), reactive oxygen species, and peroxynitrite, thereby leading to cardiac dysfunction. Nitrate tolerance increased bioavailability of NO in the heart without increasing formation of reactive oxygen species. Despite elevated myocardial NO, neither cardiac markers of peroxynitrite formation nor cardiac mechanical function were affected by nitroglycerin treatment. However, serum free nitrotyrosine, a marker for systemic peroxynitrite formation, was significantly elevated in nitroglycerin-treated animals. This is the first demonstration that, although the systemic effects of nitroglycerin may be deleterious due to enhancement of extracardiac peroxynitrite formation, nitroglycerin does not result in oxidative damage in the heart.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number1 52-1
Publication statusPublished - 2002

Fingerprint

Peroxynitrous Acid
Nitrates
Nitroglycerin
Blood Vessels
Nitric Oxide
Reactive Oxygen Species
Superoxides
Biological Availability
Mortality
Serum

Keywords

  • Myocardium
  • Nitric oxide
  • Nitroglycerin
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology

Cite this

Nitrate tolerance does not increase production of peroxynitrite in the heart. / Csont, T.; Csonka, C.; Ónody, Annamária; Görbe, A.; Dux, L.; Schulz, Richard; Baxter, Gary F.; Ferdinándy, P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 1 52-1, 2002.

Research output: Contribution to journalArticle

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AU - Ónody, Annamária

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AU - Dux, L.

AU - Schulz, Richard

AU - Baxter, Gary F.

AU - Ferdinándy, P.

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