ABSTRACT
Hemostasis depends, in part, on the ability to form a protective platelet plug in the event of vascular injury and thereby prevent excessive blood loss. A poorly controlled or excessive hemostatic response, however, can be manifested as hemorrhage or thrombosis, respectively. The primary hemostatic response is dependent upon platelets and products of the endothelium that modulate platelet function. One mediator that has been shown to have antiplatelet activity is nitric oxide (NO). Under resting conditions the endothelium is stimulated by flow to produce NO, which can regulate platelet adhesion and aggregation (Pohl and Busse, 1989; Cooke et al., 1991; de Graaf et al., 1992). The production of NO leads to activation of soluble guanylyl cyclase with a concomitant increase in cGMP, which is a principal mediator of the effects of NO. NO can inhibit platelet adhesion and aggregation, and can also induce disaggregation of previously aggregated platelets (Radomski and Moncada, 1991a,b; Radomski et al., 1987a,b,c). Thus, in different
disease states in which less or more nitric oxide is being produced by the vasculature, platelet function may be adversely altered. The platelet response may also be modulated in patients with cardiovascular disease who use organic nitrates, such as nitroglycerin, which act as NO donors. While lack of NO may lead to thrombosis, an excess of NO may be detrimental such that platelet aggregation is impaired and a bleeding diathesis results. In this chapter we will provide evidence for the importance of NO in regulating platelet function and hemostasis, and illustrate hemostatic disorders that arise when NO production or bioactivity is altered.
