Prevention of pulmonary thromboembolism by NCX 4016, a nitric oxide-releasing aspirin

We studied the antithrombotic activity of 2-acetoxybenzoate 2-[1-nitroxy-me thyl]-phenyl ester (NCX 4016), a novel nitric oxide (NO)-releasing aspirin derivative, in vivo in different animal models of platelet-dependent and in dependent pulmonary thromboembolism and compared it with that of aspirin. N CX 4016 protected mice from death induced by the intravenous (i.v.) injecti on of collagen plus epinephrine, of 9,11-dideoxy-11 alpha,9 alpha-epoxymeth ano-prostaglandin F-2 alpha (U46619) and of thrombin while aspirin was only active against collagen plus epinephrine. The drop in platelet count and n umber of lung emboli were reduced by NCX 4016 more effectively than aspirin . NCX 4016 protected mice also from mechanical pulmonary embolism (i.v. inj ection of hardened rat red blood cells) while aspirin was ineffective. In r abbits, NCX 4016 significantly reduced the accumulation of [In-111]oxine-la beled platelets in the pulmonary vasculature induced by collagen and by thr ombin while aspirin produced reductions which were significant only versus collagen. In conclusion, NCX 4016 exerts a more pronounced antithrombotic a ctivity than aspirin in vivo in two different animal species, largely due t o a deeper inhibitory effect on platelets. NCX 4016 may represent a better antithrombotic agent than aspirin. (C) 2000 Elsevier Science B.V. All right s reserved.