Effects of Nitric Oxide (NO) and Soluble Nucleoside Triphosphate Diphosphohydrolase (NTPDase) on Inhibition of Platelet Deposition In Vitro

Abstract

Vascular thrombosis is regulated via the release of several constituents from the vascular endothelium, including nucleoside triphosphate diphosphohydrolases (NTPDases or ectonucleotidases), nitric oxide (NO), and eicosanoids. Currently, it is unknown how these constituents interact in the inhibition of platelet aggregation and adhesion. To investigate the combined effects of NO and NTPDase on platelet deposition sequestration, an in vitro study was performed to compare inhibition of platelet deposition to a biomaterial by NO in the absence or presence of soluble NTPDase. Results of the platelet inhibition studies with NO and NTPDase conclusively show that the inhibitory effects of NTPDase and NO are additive. The platelet inhibitory potency in the presence of NO was enhanced by NTPDase in a dose-dependent manner, for a given NO exposure. This augmentation is independent of aspirin; the ability of NTPDase or NO alone to inhibit platelet deposition is also independent of aspirin. Clearly, NO and NTPDase independently contribute to platelet inhibition via different mechanisms. The inaction of NO on the activity of NTPDase confirmed that NO or reaction products in the presence of O 2 do not interact with NTPDase directly.