Response to Dr. Annemiek J.M. Cornelissen editorial

Excerpt

We greatly appreciate the insightful editorial response written by Dr. Cornelissen [6] in reference to our paper on 3-dimensional modeling of NO transport in a microcirculatory network [5], and certainly agree with the need to include O₂ transport and reaction in future modeling efforts. Models must eventually include interactions between NO and O₂, since: (a) O₂ is required by NO synthases (NOS) to produce NO, (b) NO reversibly inhibits tissue O₂ consumption, and (c) NO modulates blood flow and O₂ delivery through changes in smooth muscle tone. There have been relatively few O₂ transport models that incorporate reversible inhibition of O₂ consumption by NO. The first was by Thomas et al. [10], who described a model for vessels in a planar geometry. We have developed models for coupled NO and O₂ transport in cylindrical geometry for small arterioles over a wide range of conditions [1, 3, 4, 7‐9]. These models demonstrate that when the source of NO is primarily from the endothelium, O₂ consumption is inhibited to a greater extent in the region of tissue nearest the endothelium where NO levels are higher, compared with distances farther away where NO is lower due to reactions in the surrounding tissue. Even a small degree of inhibition of tissue O₂ consumption in well-oxygenated regions closest to the arteriole allows more O₂ to diffuse deeper into the surrounding tissue, preventing more hypoxic conditions at deeper locations. This effect is predicted to be even greater in models which include additional NO production in surrounding tissue by mitochondrial (mtNOS) or immune (iNOS) isoforms [4, 9]. NO production from the neuronal isoform (nNOS) in nitrergic nerves would also affect O₂ consumption. Coupled NO and O₂ transport models need to be further developed to describe vascular networks. …