Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery.
This study examined the role of platelet microparticles in thromboxane A2 (TXA2) production. Incubation of microparticles with [14C]arachidonic acid and A23187 produced 14C-labeled TXB2, the stable metabolite of TXA2. To investigate the possibility that endothelial cells (ECs) transfer arachidonic acid to platelet microparticles and promote TXB2 synthesis, ECs with their cellular lipids prelabeled with tritiated arachidonic acid were incubated with microparticles. In the absence of microparticles, there was no production of tritiated TXB2 by the ECs. However, when microparticles were coincubated with prelabeled ECs, tritiated arachidonic acid was metabolized to tritiated TXB2. Aspirin was then used to inhibit cyclooxygenase. ECs coincubated with aspirin-treated platelet microparticles did not produce TXB2, as measured by radioimmunoassay. In contrast, aspirin-treated ECs coincubated with microparticles produced TXB2, and its production was enhanced by methacholine (10(-4) mol/L), indicating that endothelially derived arachidonic acid, and not endothelially derived prostaglandin endoperoxide, was transferred to the microparticle and further metabolized to TXA2. Additional studies with rabbit aorta and pulmonary artery investigated whether microparticles contributed to vascular contractions. Preincubation with microparticles enhanced arachidonic acid-induced contractions in the aorta and methacholine-induced contractions in the pulmonary artery. The thromboxane receptor antagonist SQ29548 and the thromboxane synthase inhibitor dazoxiben blocked these effects. Because TXA2 is an important mediator in various pathophysiologic states, including hypertension, the ability of platelet microparticles to act as a cellular source of TXA2 might provide new insight into the role of platelets and platelet microparticles in the control of vascular tone.
Pfister
Sandra L
SL
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. spfister@mcw.edu
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011817:Rabbits; D013928:Thromboxane A2 / Q000096:biosynthesis*; D014661:Vasoconstriction
D016718:Arachidonic Acid; D013928:Thromboxane A2