Nitric Oxide and Platelet Function.

Nitric Oxide (NO) is a versatile messenger molecule of the vascular system. Three different NO synthase (NOS) isoforms found in the vasculature can synthesize NO: endothelial NOS, neuronal NOS, and inducible NOS. Once produced, NO can diffuse across cell membranes and modulate the cell biology of leukocytes, endothelial cells, and platelets. NO has several classes of molecular targets, including proteins with heme moieties, such as guanyly cyclase, cysteine residues of proteins, and radicals, such as superoxide. NO influences platelets through at least two distinct pathways. NO activation of a cGMP pathway mediates NO inhibition of eicosanoid metabolism, NO suppression of gpIIb/IIIa conformational changes, and NO deactivation of thromboxane receptors. However, NO also regulates platelets by chemically modifying cysteine residues of proteins critical to platelet activation. For example, NO modifies key cysteine residues of the enzyme N-ethylmaleimide sensitive factor, thereby blocking exocytosis of alphagranules. Recent studies have shown that metabolites of NO such as nitrite may also regulate platelet function.