Nitric Oxide: An Introductory Primer.

As humans evolved in an atmosphere in which the most plentiful gases are Nitrogen and Oxygen, it is not surprising that nitric oxide (NO) plays an important role in human physiology. Originally described as an “endothelial relaxing factor,” we now recognize NO as not only a neurotransmitter, but also an important agent in blood physiology and vascular biology. In this symposium, three experts in NO research discuss emerging knowledge of NO’s role in hematology and transfusion medicine. NO is derived from arginine by three isoforms of NO synthetase, including NOS₃ found in endothelial cells. NO binds avidly to free hemoglobin (Hg) through several chemical interactions, some of which depend upon the degree of oxygen saturation of Hg. Scavenging of NO by free plasma Hg accounts for the hypertensive effects of RBC substitutes and likely contributes to the renal lesion that accompanies acute hemolytic transfusion reactions. Under non-hemolytic conditions, the RBC membrane plays an important role to limit scavenging of endothelial-derived NO by Hg. The importance of disrupted NO physiology is exemplified by sickle cell anemia, in which chronic intravascular hemolysis, abnormal hemoglobin shape change during deoxygenation, and membrane abnormalities may all contribute to the disruption of NO physiology. Reduced NO in sickle cell anemia may contribute pulmonary hypertension, right ventricular strain, vasculopathy, and thrombosis. A better understanding of the role of NO in sickle cell anemia holds promise for new therapeutic approaches to this devastating blood disorder. Recent research is exploring changes in the concentration of NO that occur in stored red cells prior to and following transfusion. Whether or not these changes may account for clinical effects of blood transfusion is an area of active investigation. NO also plays a fundamental role in platelet physiology where it serves to reduce platelet activation. Thus, depletion of NO during intravascular hemolysis promotes a thrombotic signal. Examples may include TTP, transfusion reactions, PNH, DIC, sickle cell anemia, and others. The molecular mechanism of NO’s action on platelets, including its effects on vesicle and protein trafficking within the cell, is the subject of active research that will be summarized. Attendees of this symposium should gain new insights into the important role that NO plays in blood, vascular, and transfusion physiology.