Effects of AVS (1,2-bis(nicotinamido)propane) on platelet function and vascular endothelium.
The effects of 1,2-bis(nicotinamido)propane (AVS) on platelet function and vascular endothelium were investigated using various experimental thrombosis and vascular endothelial injury models. Neither in vitro platelet aggregation induced by ADP, collagen or arachidonate nor ex vivo platelet aggregation by ADP or collagen could be antagonized by AVS. On the other hand, AVS prevented mice, rats and rabbits from death induced by acute cerebral or pulmonary thromboembolism following the injection of arachidonate or collagen. These activities were as potent as those of acetylsalicylic acid. The disrupting actions of citrate and/or lipidperoxide (13-hydroperoxy linoleic acid) on endothelium were well inhibited by the pretreatment of AVS. AVS did not inhibit cyclooxygenase, increased prostacyclin (PGI2)/thromboxane A2 (TXA2) ratio in the coupled system of platelets and aortic microsomes. In conclusion, AVS inhibited thrombus formation in vivo while it was ineffective in vitro platelet alone system, which may result from the actions of this agent on both platelets and vascular endothelium. The above-mentioned results clearly show that AVS may be a new potent anti-vascular damaging agent with both endothelium stabilizing and PGI2 enhancing activities.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000633:toxicity; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000188:drug therapy; D003094:Collagen / Q000633:toxicity; D015232:Dinoprostone; D004727:Endothelium / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013923:Thromboembolism / Q000139:chemically induced / Q000188:drug therapy; D013927:Thrombosis / Q000503:physiopathology; D013928:Thromboxane A2 / Q000494:pharmacology
D001095:Arachidonic Acids; D011458:Prostaglandins E; D009536:Niacinamide; D016718:Arachidonic Acid; D013928:Thromboxane A2; D003094:Collagen; D015232:Dinoprostone; D001241:Aspirin; C042625:nicaraven