NITRIC OXIDE AND SICKLE CELL-ASSOCIATED CARDIOPULMONARY DISORDERS

Sickle cell disease (SCD) is a genetic blood disorder characterized by the presence of sickleshaped red blood cells (RBCs), which cause impaired blood flow and lead to various systemic complications, particularly within the cardiovascular and pulmonary systems. Nitric oxide (NO), a critical vasodilator, plays a significant role in maintaining vascular homeostasis, including regulating blood vessel tone, preventing platelet aggregation, and promoting smooth muscle relaxation. In SCD, decreased NO bioavailability due to increased oxidative stress, hemolysis, and arginase activity results in endothelial dysfunction, contributing to the development of pulmonary hypertension (PH), right heart failure, and other cardiopulmonary complications. The dysregulation of NO in SCD leads to a cascade of pathophysiological changes in the vascular system, primarily affecting the pulmonary vasculature. Impaired NO signaling exacerbates pulmonary vasoconstriction and endothelial injury, which increase pulmonary vascular resistance and promote PH. Additionally, the reduction in NO levels is associated with right heart failure, as the right ventricle faces increased afterload. The combination of PH and right heart failure significantly affects the morbidity and mortality of individuals with SCD, highlighting the importance of NO in the management of these complications.