[Experimental antithrombotic activity of oral isosorbide dinitrate].
The activity of isosorbide dinitrate (ISDN) a nitrate derivative with platelet anti-aggregant properties, was studied on a model of arterial thrombosis by electric stimulation of the rat carotid arteries. In control animals, occlusive thrombosis occurred in 15.3 +/- 1.0 minutes. When administered orally in dosages of 1 to 30 mg/kg, 30 minutes before stimulation, ISDN prolonged the time to arterial occlusion by a factor of 2 to 3 times. This effect was significant from doses of 1 mg/kg. This anti-thrombotic activity was unchanged by pretreatment of 100 mg/kg I.V. of acetylsalicylic acid, a dose sufficient to inhibit prostacycline synthesis. On the other hand, its activity was completely blocked by the administration of an inhibitor of NO-synthetase, L-nitroarginine methylester (1 mg/kg I.V.). These results show that ISDN is active on a model of arterial thrombosis in the rat by a mechanism independent of prostacycline production but implying a stimulation of the formation of nitric oxide.
Plotkine
M
M
Laboratoire de pharmacologie, université René-Descartes, Paris.
Allix
M
M
Guillou
J
J
Boulu
R
R
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012107:Research Design; D013927:Thrombosis / Q000503:physiopathology
D010975:Platelet Aggregation Inhibitors; D001120:Arginine; D007548:Isosorbide Dinitrate; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester
Activité antithrombotique expérimentale du dinitrate d'isosorbide administré par voie orale.