Modeling of endothelial nitric oxide production and diffusion

Nitric oxide (NO) produced by the vascular endothelium is an important biological messenger which regulates vessel tone and permeability as well as inhibits platelet adhesion and aggregation. Therefore, diffusion of NO to the target cells becomes an important factor for NO to exert its biological actions. However, this issue has not been carefully examined. Previous analyses on NO diffusion using a point-source approximation may be invalid in the vicinity of a macroscopic source. Furthermore, the effects of the reaction order of the lumped NO consumption reactions and the geometry of the NO source have not been investigated. By using a continuum approach in which NO is produced by a surface reaction, the NO production and consumption around the endothelium of a blood vessel and in monolayer cultures are modeled. Experimental data from the literature are used to estimate the NO production and consumption rates. Modeling results show that the concentration profile is strongly influenced by the order of the lumped NO consumption reaction, the distribution of NO production between the luminal and abluminal surfaces of the endothelium, and by the presence of a thin, erythrocyte free layer adjacent to the endothelium. Moreover, the NO concentration in endothelial cells may be significantly higher for cultured cells than those in intact vessels. The approach presented here provides a framework for modeling of endothelial NO production and its diffusion through surrounding tissue.

Modeling of endothelial nitric oxide production and diffusion Academic Article