Potential role of transport in the affect of nitric oxide on thrombus formation

Activated platelets synthesize and secrete a number of substances that activate other platelets, cause smooth muscle cell (SMC) constriction, and promote SMC proliferation. In contrast, platelets synthesize nitric oxide (NO), which is a potent platelet inhibitor, a SMC relaxer, and a SMC proliferation inhibitor. Whereas NO must have a mediating effect on coagulation, it is not clear why it is necessary to have this type of negative feedback in the fundamentally positive feedback-based coagulation cascade. It is proposed here that the unique diffusion characteristics of NO cause this molecule to be not just a global inhibitor of platelet activity, but rather an inhibitor at specific local regions. This effect would allow the initial growth of the thrombus, but would limit that growth to a confined area. To examine this hypothesis, a simple model for platelet release, platelet synthesis, and agonist/inhibitor transport has been developed. The results suggest that NO's effect is unimportant during the early part of clot formation, but becomes more important later in the process.