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Am J Physiol Heart Circ Physiol 283: H69-H76, 2002. First published February 28, 2002; doi:10.1152/ajpheart.00817.2001
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Vol. 283, Issue 1, H69-H76, July 2002

Nitrate tolerance does not increase production of peroxynitrite in the heart

Tamás Csont1, Csaba Csonka1, Annamária Ónody1, Anikó Görbe1, László Dux1, Richard Schulz2, Gary F. Baxter3, and Péter Ferdinandy1

1 Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, H-6720, Hungary; 2 Cardiovascular Research Group, Departments of Pharmacology and Pediatrics, University of Alberta, Edmonton, Alberta, Canada T6G 2R7; and 3 The Royal Veterinary College, University of London, London NW1 0TU, United Kingdom

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.

nitroglycerin; nitric oxide; reactive oxygen species; myocardium


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