Nitric Oxide Inhalation Inhibits Platelet Aggregation and Platelet-Mediated Pulmonary Thrombosis in Rats

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 comp...