Role of Platelet Microparticles in the Production of Thromboxane by Rabbit Pulmonary Artery
- 1 February 2004
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 43 (2), 428-433
- https://doi.org/10.1161/01.hyp.0000110906.77479.91
Abstract
This study examined the role of platelet microparticles in thromboxane A 2 (TXA 2 ) production. Incubation of microparticles with [ 14 C]arachidonic acid and A23187 produced 14 C-labeled TXB 2 , the stable metabolite of TXA 2 . To investigate the possibility that endothelial cells (ECs) transfer arachidonic acid to platelet microparticles and promote TXB 2 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 TXB 2 by the ECs. However, when microparticles were coincubated with prelabeled ECs, tritiated arachidonic acid was metabolized to tritiated TXB 2 . Aspirin was then used to inhibit cyclooxygenase. ECs coincubated with aspirin-treated platelet microparticles did not produce TXB 2 , as measured by radioimmunoassay. In contrast, aspirin-treated ECs coincubated with microparticles produced TXB 2 , 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 TXA 2 . 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 TXA 2 is an important mediator in various pathophysiologic states, including hypertension, the ability of platelet microparticles to act as a cellular source of TXA 2 might provide new insight into the role of platelets and platelet microparticles in the control of vascular tone.Keywords
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