Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics.

Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in neurovascular coupling. NO produced by neurons diffuses into the smooth muscle surrounding cerebral arterioles, driving vasodilation. However, the rate of NO degradation in hemoglobin is orders of magnitude higher than in brain tissue, though how this might impact NO signaling dynamics is not completely understood. We used simulations to investigate how the spatial and temporal patterns of NO generation and degradation impacted dilation of a penetrating arteriole in cortex. We found that the spatial location of NO production and the size of the vessel both played an important role in determining its responsiveness to NO. The much higher rate of NO degradation and scavenging of NO in the blood relative to the tissue drove emergent vascular dynamics. Large vasodilation events could be followed by post-stimulus constrictions driven by the increased degradation of NO by the blood, and vasomotion-like 0.1–0.3 Hz oscillations could also be generated. We found that these dynamics could be enhanced by elevation of free hemoglobin in the plasma, which occurs in diseases such as malaria and sickle cell anemia, or following blood transfusions. Finally, we show that changes in blood flow during hypoxia or hyperoxia could be explained by altered NO degradation in the parenchyma. Our simulations suggest that many common vascular dynamics may be emergent phenomena generated by NO degradation by the blood or parenchyma. Author summary: Nitric oxide (NO) generated by neurons during states of increased neural activity dilates arteries, increasing local cerebral blood flow. Scavenging of nitric oxide is much more rapid in the blood than in the tissue, but how the dynamics of NO production and degradation affect the coupling between neural activity and vasodilation is not understood. Here we used computer simulations to model how nitric oxide produced by neurons leads to changes in arteriole size. We find that because nitric oxide is removed from the brain by the blood, changes in arteriole size or blood composition play a role in shaping neurally evoked changes in cerebral blood flow. As the arteriole dilates and supplies more blood, nitric oxide is removed by the blood at a faster rate and this interaction is able to reproduce many commonly observed arteriole dynamics. These dynamics can also be affected by pathologies where blood cells break down, providing a potential link between the state of the blood and blood flow dynamics in the brain. [ABSTRACT FROM AUTHOR]