Effect of serotonergic antagonism on local responses to an acute and selective endothelial trauma in vivo.
Serotonin is liberated during platelet release reaction. It is concluded from in vitro experiments that serotonin influences both platelet activation and thrombus-induced vasoconstriction. The subject of the present study was to assess the impact of the serotonin2 antagonist naftidrofuryl on both thrombogenesis and thrombus-induced vasoconstriction in vivo. In a hamster cheek pouch, vessels form a rich meshwork, allowing repetitive experiments to obtain intraindividual control measurements. With a contactless photochemical process, endothelial cells can be damaged in vivo. Regularly platelets and the coagulation system are activated and thrombi are formed. In larger arterial vessels local vasoconstriction occurs. Thrombogenesis was induced in arterioles with an inner diameter between 17 and 20 microns. It was monitored by the continuous measurement of blood cell velocity to assess initial hemodynamics and the interval elapsing until perfusion stops. Solvent alone had no effect. Naftidrofuryl was given in clinically relevant dosages of 1, 5, and 20 mg/kg intra-arterially. Even 1 mg/kg showed a significant antithrombotic effect. Efficacy increased in a dose-related manner as well as during the time interval of observation (i.e., 2 h after application). As an established antithrombotic standard, acetylsalicylic acid was applied in dosages of 10 and 100 mg/kg. Both dosages were found to be antithrombotic, but not more effective than comparable dosages of naftidrofuryl. Larger arterioles with an inner diameter of about 50 microns have smooth muscle cells. They constrict during thrombogenesis as a local response to substances released by the thrombus. Topical application of papaverine abolished vasoconstriction. A thromboxane antagonist (EP092) was also effective. Naftidrofuryl reduced the vasoconstriction whereas its solvent was without effect.
Department of Cardiology, University of Göttingen, F.R.G.
K S
KS
Herrmann
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H
Kreuzer
D000208:Acute Disease; D000818:Animals; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects*; D008647:Mesocricetus; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013927:Thrombosis / Q000188:drug therapy*
D012702:Serotonin Antagonists