© 1997 American Heart Association, Inc.
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Nitric Oxide Inhalation Inhibits Platelet Aggregation and Platelet-Mediated Pulmonary Thrombosis in Rats
From the Center for Transgene Technology and Gene Therapy (Z.N., D.C.), Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium, and the Center for Molecular and Vascular Biology (M.H.) and Department of Cardiology (N. Van P., S.J.), University Hospital Gasthuisberg, University of Leuven.
Correspondence to Stefan Janssens, MD, PhD, Center for Transgene Technology and Gene Therapy and Department of Cardiology, University Hospital Gasthuisberg, 49 Herestraat, B-3000 Leuven, Belgium. E-mail stefan.janssens{at}med.kuleuven.ac.be
Abstract Endothelium-derived nitric oxide (NO) inhibits in vitro platelet aggregation via a cGMP-dependent mechanism. The effect of inhaled NO on platelet-mediated pulmonary thrombosis following intravenous thrombotic challenge with collagen was examined in rats and compared with the effect of G4120, a cyclic Arg-Gly-Asp–containing synthetic pentapeptide that binds to the platelet glycoprotein IIb/IIIa receptor. Intraplatelet cGMP dose-dependently increased from 39±6 fmol/108 platelets in control to 46±6, 68±13, and 81±13 fmol/108 platelets after inhalation with 20, 40, and 80 ppm NO, respectively (P<.05 for 40 and 80 ppm). Ex vivo platelet aggregation of platelet-rich plasma induced by 1 µg/mL collagen was reduced from 75±4% in control rats to 22±10% and 20±7% in rats ventilated with 40 and 80 ppm NO, respectively, and to 30±9% in G4120-treated rats (each P<.05 versus control). Circulating platelet counts 3 minutes after collagen injection were significantly higher in the inhaled NO and G4120 groups compared with control rats (250 000±18 000 and 223 000±10 000/µL versus 160 000±18 000/µL, each P<.05). The rise in pulmonary arterial pressure after collagen injection was significantly reduced in NO- and G4120-treated rats (26±1 and 27±1 versus 32±1 mm Hg in control rats, each P<.05). The number of pulmonary resistance vessels containing platelet thrombi was significantly smaller after inhaled NO and G4120 treatment compared with control (56±3% and 50±3% versus 68±3%, respectively; P<.05). Thus, NO inhalation reduces in vivo activation of circulating platelets and platelet-rich thrombosis in thromboembolic pulmonary hypertension. Inhalation of NO may be useful in cardiovascular diseases associated with platelet activation.
Key Words: pulmonary thromboembolism • platelet aggregation • nitric oxide
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