DEFIBROTIDE MEDIATED INHIBITION OF SEROTONIN, ENDOTHELIN-I, THROMBOXANE, AND SERUM-INDUCED CONTRACTION OF CANINE FEMORAL AND PULMONARY ARTERIAL RINGS

Defibrotide is a polydeoxyribonucleotide derived agent with a weight a verage of 15 to 18 kDa. By virtue of its chemical nature, this polyele ctrolyte agent exerts multiple pharmacologic actions at various plasma tic and cellular sites. In recent studies, this agent has been demonst rated to exhibit cardioprotective and vasomodulatory actions. To test the effect of defibrotide on the vascular smooth muscle contractile re sponses, its effects were evaluated on contractile response induced by agonists in canine femoral and pulmonary arterial smooth muscle prepa ration. These arterial preparations were harvested from anesthetized a nd anticoagulated (Heparinized 3-5 U/ml) dogs. Defibrotide was adminis tered to dogs at 10 mg/kg, i.v. and segments of canine arteries were h arvested at 30 minutes after the administration of this agent. The con trol and defibrotide treated canine arterial ring preparations were te sted against serotonin, endothelin-I, serum and control platelet rich plasma(PRP) with arachidonic acid(AA). The contractile response of art erial rings obtained for treated groups were measured using serotonin, endothelin-I, serum and PRP/AA as agonists. The contractile action of serotonin, endothelin-I, serum and PRP/AA were inhibited by pretreatm ent of the animal with defibrotide. The arterial ring isolated from do gs treated with defibrotide exhibited a weaker contraction. These stud ies support the hypothesis that defibrotide modulates endothelial func tion and the response to the contractile actions of various agonists m ay be related to this effect. Copyright (C) 1996 Elsevier Science Ltd