Consequences of low nitric oxide (NO) bioavailability. The consequences of decreased NO bioavailability include endothelial cell activation, upregulation of the potent vasoconstrictor endothelin-1, vasoconstriction, platelet activation, increased tissue factor and activation of coagulation pathways, all of which ultimately translates into the clinical manifestations of sickle cell disease. NO bioavailability is particularly vulnerable to the effects of hemolysis, an event in sickle cell disease that contributes to the development of the hemolytic subphenotypes, which include pulmonary hypertension, priapism, cutaneous leg ulceration, stroke and possibly asthma.