Effect of free hemoglobin on NO bioavailability in microcirculation: A computational model

Hemolytic anemias, including sickle cell disease and thalassemia, reportedly lead to cardiopulmonary complications such as pulmonary and systemic hypertension, and endothelial dysfunction. Hemolytic anemias are characterized by intravascular hemolysis which results in release of small amounts of free hemoglobin (Hb) in the vascular lumen. Cell free Hb is an effective scavenger of endothelium‐derived vasodilator nitric oxide (NO) (k~10 7 M −1 s −1 ). In this study, we used a recently published 2‐dimensional mathematical model (Deonikar and Kavdia, 2010, doi:10.1016/j.mvr.2010.09.004) representing NO transport in an arteriole to understand the effect of small amounts of intravascular Hb on NO bioavailability in the vascular lumen as well as vascular wall. The model parameters were chosen to represent sickle cell disease conditions. In presence of 4 μM cell free Hb, we found that the endothelial NO levels decreased ~2–5 times and the smooth muscle cell NO levels decreased ~3–7.5 times as compared with respective NO levels in absence of cell free Hb. Lowered NO bioavailability in presence of cell free hemoglobin may explain the endothelial dysfunction and hypertension observed in hemolytic anemias.