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: A Mogielnicki, K Kramkowski, L Pietrzak, W Buczko
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 58 Issue 3 Pg. 515-27 (Sep 2007) ISSN: 0867-5910 [Print] Poland
• PMID: 17928647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Platelet Aggregation Inhibitors
• Niacinamide
• 6-Ketoprostaglandin F1 alpha
• Collagen
• Epoprostenol
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester
• N-methylnicotinamide
• Indomethacin

Topics

• 6-Ketoprostaglandin F1 alpha (metabolism)
• Animals
• Blood Flow Velocity (drug effects)
• Blood Pressure (drug effects)
• Carotid Arteries (drug effects, physiopathology)
• Collagen (adverse effects, antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Epoprostenol (antagonists & inhibitors)
• Fibrinolysis (drug effects)
• Heart Rate (drug effects)
• Hypertension, Renal (complications, physiopathology)
• Indomethacin (pharmacology)
• Injections, Intravenous
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Niacinamide (administration & dosage, analogs & derivatives, pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (pharmacology)
• Rats
• Rats, Wistar
• Thrombosis (complications, metabolism, prevention & control)