[The vascular effects of thrombin on canine and human arteries; their independence from the metabolism of arachidonic acid].
Independently of it's effects on the coagulation cascade, thrombin can interact with the endothelium and release vasodilatory mediators as prostacyclin, endothelium dependent relaxing factor and potentiate the vascular changes induced by vasoconstrictors like endothelin or cathecolamines. Therefore, in the present study we tested the effect of thrombin in the pulmonary and femoral canine arteries and compared it with the effects on human umbilical artery; we also explore the possible mechanism of action of thrombin-induced changes in vascular tone by using specific inhibitors. Thrombin induced a concentration-dependent and endothelium-dependent relaxation on canine arteries (pulmonary or femoral) and endothelium-independent contraction of human umbilical arteries, neither the relaxation nor the contraction were significantly affected by incubation of the vessels with: a cyclooxygenase inhibitor (indomethacin), lypooxygenase inhibitor (BW 755C) or a soup of antagonists (atropine, metysergyde, propanolol, meperamine or phenoribenzamine) to block muscarinic, histaminic, serotoninergic or adrenergic receptors. However, incubation of the vessels with heparin or a calcium channel blocker did prevented the vasoconstrictor effect of thrombin in human umbilical veins. This results suggests that thrombin can elicit changes in vascular tone and the effect is dependent of the vessel stimulated, and the presence of the endothelium. Thus, thrombin-dependent change in vascular tone is not mediated by arachidonic acid metabolites, sympathetic or parasympathetic neurotransmitters, histamine or serotonine receptors. Thrombin effects may be mediated by interaction with an specific receptor coupled with a calcium signal.
Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, INCICH, México, D.F.
B A
BA
Escalante Acosta
J L
JL
Amezcua Gastelum
I
I
Aldana Alcalá
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects* / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
D016718:Arachidonic Acid; D013917:Thrombin
Efectos vasculares de la trombina en arterias caninas y humana; su independencia del metabolismo del ácido araquidónico.