Correspondence  |   May 2009
Nitric Oxide Metabolites, Platelet Activation, and Myocardial Ischemia Reperfusion Injury
Author Affiliations & Notes
  • Peter Rosenberger, M.D., Ph.D.
  • *Tübingen University Hospital, Tübingen, Germany.
Article Information
Correspondence   |   May 2009
Nitric Oxide Metabolites, Platelet Activation, and Myocardial Ischemia Reperfusion Injury
Anesthesiology 5 2009, Vol.110, 1198-1199. doi:
Anesthesiology 5 2009, Vol.110, 1198-1199. doi:
To the Editor:—
We read with great interest the research article by Nagasaka et al.  demonstrating a role of nitric oxide and its metabolites in the systemic circulation.1 As the authors impressively demonstrate, active nitric oxide metabolites are carried into the systemic circulation where they accumulate in the blood and in the heart, and as a result have significant impact on the extent of myocardial ischemia reperfusion injury.
Nitric oxide induces cyclic guanosine phosphatase activation and increases cyclic guanosine monophosphate levels in several tissues, including platelets. Several investigators have demonstrated that this is caused not only by endogenous nitric oxide with significant impact on platelet activity, but also by inhalative nitric oxide.2,3 The crucial importance of platelets and the activity state of platelets on the extent of myocardial ischemia reperfusion injury was outlined by previous investigations.3–5 A downstream target of cyclic guanosine phosphatase activation in platelets is vasodilator-stimulated phosphoprotein (VASP), a central cytoskeletal binding protein.6 The intracellular increase in cyclic guanosine phosphatase results in a phosphorylation of VASP, which is a crucial step in the control of platelet activity. Clinically, the extent of VASP phosphorylation is used to monitor the success of an anticoagulatory therapy, as during clopidogrel therapy, and reflects the success of platelet activation during an anticoagulatory therapy.7 
Therefore we were wondering whether the authors think that VASP phosphorylation could be a useful monitor in their experimental system, and whether the monitoring the extent of VASP phosphorylation could be a valuable tool to monitor the clinical effectiveness if an inhaled nitric oxide therapy.
*Tübingen University Hospital, Tübingen, Germany.
Nagasaka Y, Fernandez BO, Garcia-Saura MF, Petersen B, Ichinose F, Bloch KD, Feelisch M, Zapol WM: Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury. Anesthesiology 2008; 109:675–82Nagasaka, Y Fernandez, BO Garcia-Saura, MF Petersen, B Ichinose, F Bloch, KD Feelisch, M Zapol, WM
Gries A, Bode C, Peter K, Herr A, Böhrer H, Motsch J, Martin E: Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding in vitro  and in vivo  . Circulation 1998; 97:1481–7Gries, A Bode, C Peter, K Herr, A Böhrer, H Motsch, J Martin, E
Radomski MW, Palmer RM, Moncada S: Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 1987; 92:181–7Radomski, MW Palmer, RM Moncada, S
Massberg S, Grüner S, Konrad I, Garcia Arguinzonis MI, Eigenthaler M, Hemler K, Kersting J, Schulz C, Muller I, Besta F, Nieswandt B, Heinzmann U, Walter U, Gawaz M: Enhanced in vivo  platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)-deficient mice. Blood 2004; 103:136–42Massberg, S Grüner, S Konrad, I Garcia Arguinzonis, MI Eigenthaler, M Hemler, K Kersting, J Schulz, C Muller, I Besta, F Nieswandt, B Heinzmann, U Walter, U Gawaz, M
Davì G, Patrono C: Platelet activation and atherothrombosis. N Engl J Med 2007; 357:2482–94Davì, G Patrono, C
Li Z, Ajdic J, Eigenthaler M, Du X: A predominant role for cAMP-dependent protein kinase in the cGMP-induced phosphorylation of vasodilator-stimulated phosphoprotein and platelet inhibition in humans. Blood 2003; 101:4423–9Li, Z Ajdic, J Eigenthaler, M Du, X
Geiger J, Brich J, Hönig-Liedl P, Eigenthaler M, Schanzenbächer P, Herbert JM, Walter U: Specific impairment of human platelet P2Y(AC) ADP receptor-mediated signaling by the antiplatelet drug clopidogrel. Arterioscler Thromb Vasc Biol 1999; 19:2007–11Geiger, J Brich, J Hönig-Liedl, P Eigenthaler, M Schanzenbächer, P Herbert, JM Walter, U