title: N-methylnicotinamide inhibits arterial thrombosis in hypertensive rats.
abstract: There are few findings indicating that nicotinamide may potentially influence intravascular thrombosis. Interestingly, N-methylnicotinamide, one of the metabolites of nicotinamide - could be more potent than its parent compound. In the present study we have investigated the influence of N-methylnicotinamide on arterial thrombosis in normotensive and renovascular hypertensive rats. The contribution of platelets, coagulation and fibrinolytic systems in the mode of N-methylnicotinamide action was also determined. Furthermore, we examined the role of nitric oxide/prostacyclin in the mechanisms of N-methylnicotinamide action. N-methylnicotinamide, but not nicotinamide, administered intravenously into renovascular hypertensive rats developing electrically induced arterial thrombosis caused dose-dependent decrease of thrombus weight, collagen-induced platelet aggregation and plasma antigen/activity of plasminogen activator inhibitor - 1, without changing of occlusion time, routine coagulation parameters and plasma activity of tissue plasminogen activator. Indomethacin - an inhibitor of prostacyclin synthesis, completely abolished the antithrombotic and antiplatelet effect of N-methylnicotinamide, and the plasma level of 6-keto-PGF(1alpha) , prostacyclin metabolite, increased simultaneously with the inhibition of thrombus formation. Our study shows that N-methylnicotinamide via production/release of prostacyclin inhibits arterial thrombosis development. The antithrombotic effect of N-methylnicotinamide is accompanied by platelet inhibition and enhanced fibrinolysis, due to the decrease production of plasminogen activator inhibitor - 1.
authors.affiliation: Department of Pharmacodynamics, Medical University in Bialystok, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Mogielnicki
authors.forename: K
authors.initials: K
authors.lastname: Kramkowski
authors.forename: L
authors.initials: L
authors.lastname: Pietrzak
authors.forename: W
authors.initials: W
authors.lastname: Buczko
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D003094:Collagen / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000037:antagonists & inhibitors; D005342:Fibrinolysis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000150:complications* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D010975:Platelet Aggregation Inhibitors; D009536:Niacinamide; D015121:6-Ketoprostaglandin F1 alpha; D003094:Collagen; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; C008472:N-methylnicotinamide; D007213:Indomethacin