Date of Award
Doctor of Philosophy (PhD)
Steven A. Jones
Nitric oxide (NO) has been shown to suppress platelet activation, induce vasodilation, inhibit smooth muscle cell proliferation, and act against infection. Activated platelets generally have opposite effects from these. They secrete platelet-derived growth factor (PDGF), which stimulates smooth muscle growth, serotonin, which is a platelet agonist, and a number of agents that promote further platelet aggregation. However, activated platelets also produce NO through the enzymatic functions of the constitutive form of nitric oxide synthase (NOS). The primary functions of this capability are not yet completely understood. Due to its low molecular weight and high diffusivity, NO is quickly transported from its source to surrounding tissues and medium, and this characteristic may be instrumental to its function. Understanding the way in which NO interacts with platelet function could assist in the development of improved diagnostic and surgical procedures as well as biomaterials that are resistant to thrombus formation. Due to the short half-life of NO in vivo and in vitro, it was desired to use platelet-derived serotonin and an indicator for NO function. The research objectives for this project were (1) to develop mathematical models representing the diffusive transport of platelet derived agonists and inhibitors, (2) to electrochemically measure serotonin concentration during in vitro aggregation of platelets to fibrillar collagen with and without L-NMMA (a NO inhibitor), and (3) to verify platelet aggregation through histological analysis.
Presence of the NOS inhibitor, L-NMMA, did not have a statistical significance when compared across experiments with fibrillar collagen, which lacked L-NMMA. It can be inferred from this analysis that a statistically significant change in serotonin concentration, resulting from platelet activation by collagen, could not be detected when compared in presence and absence of the NOS inhibitor L-NMMA. From the research conducted in this project, many questions have been postulated concerning the primary role of NO in platelet function.
Frilot, Clifton Ford II, "" (2001). Dissertation. 722.