Unexpected, tolerance-devoid vasomotor and platelet actions of pentaerythrityl tetranitrate

Journal of Cardiovascular Pharmacology
B Fink, E Bassenge

Abstract

Efficacy of nitrate therapy is limited by tolerance. A surprising upregulation of ex vivo platelet activity, a decrease in platelet thiol levels, and an enhanced release of vasoconstrictors from platelets is associated with enhanced superoxide-mediated oxidant stress leading to vascular tolerance to nitrates. We tested the NO-donor pentaerythrityl tetranitrate (PETN), which to date had not been precisely tested either with regard to the induction of tolerance or to a potential development of changes in platelet activity in comparison with glycerol trinitrate (GTN). Long-term instrumented dogs nonintermittently received: 1.5 microg/kg/min GTN, i.v., with or without vitamin C (55 microg/kg/min, i.v.) or PETN 4 x 60 mg/day orally for 5 days. Tested daily were (a) the dilation of the epicardial arteries, (b) thrombin-induced (0.5 U/ml) increases of the intracellular Ca2+ concentration and aggregability of platelets, (c) concentrations of reduced low-molecular-weight thiols (LMTs) in plasma and platelets, and (d) formation of reactive oxygen species (ROSs). During nonintermittent PETN and during GTN with additional vitamin C, a 9.8 +/- 0.4% coronary artery dilation was observed in contrast to that with GTN alone, which resulted in c...Continue Reading

References

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Citations

Dec 22, 1999·Journal of Cardiovascular Pharmacology·B FinkE Bassenge
Jul 11, 2001·Journal of Cardiovascular Pharmacology·M SchwemmerB Fink
May 6, 2009·Clinical and Experimental Pharmacology & Physiology·Darren C HenstridgeBronwyn A Kingwell
Jul 3, 1998·The Journal of Clinical Investigation·E BassengeB Fink
Feb 1, 2002·Biochemical and Biophysical Research Communications·Stefanie OberleHenning Schröder
Mar 27, 2009·Journal of Cellular and Molecular Medicine·Marc OppermannGeorg Kojda
Sep 8, 2010·Pharmazie in unserer Zeit·Andreas DaiberThomas Münzel
Dec 4, 2003·Journal of the American College of Cardiology·John D Parker
Jun 4, 2005·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·M GerováM Cebová
Dec 16, 2010·Molecular Pharmacology·Martina GriesbergerBernd Mayer
Apr 24, 2003·Experimental Biology and Medicine·Stefanie OberleHenning Schröder
Jan 31, 2009·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Tommaso Gori, Andreas Daiber
Apr 11, 2002·Chemical Reviews·Peng George WangAdam J Janczuk
Jul 16, 1999·Biochemical and Biophysical Research Communications·S OberleH Schröder

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