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Contribution of nNOS- and eNOS-derived NO to microvascular smooth muscle NO exposure

¹Biomedical Engineering Program, University of Arkansas, Fayetteville, Arkansas 72701; and ²Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205

Submitted 16 January 2004 ; accepted in final form 15 March 2004

Nitric oxide (NO) plays an important role in autocrine and paracrine manner in numerous physiological processes, including regulation of blood pressure and blood flow, platelet aggregation, and leukocyte adhesion. In vascular wall, most of the bioavailable NO is believed to derive from endothelial cell NO synthase (eNOS). Recently, neuronal NOS (nNOS) has been identified as a source of NO in the vicinity of microvessels and has been shown to participate in vascular function. Thus NO can be produced and transported to the vascular smooth muscle cells from 1) endothelial cells and 2) perivascular nerve fibers, mast cells, and other nNOS-containing sources. In this study, a mathematical model of NO diffusion-reaction in a cylindrical arteriolar segment was formulated. The model quantifies the relative contribution of these NO sources and the smooth muscle availability of NO in a tissue containing an arteriolar blood vessel. The results indicate that a source of NO derived through nNOS in the perivascular region can be a significant contributor to smooth muscle NO. Predicted smooth muscle NO concentrations are as high as 430 nM, which is consistent with reported experimental measurements (400 nM). In addition, we used the model to analyze the smooth muscle NO availability in 1) eNOS and nNOS knockout experiments, 2) the presence of myoglobin, and 3) the presence of cell-free Hb, e.g., Hb-based oxygen carriers. The results show that NO release by nNOS would significantly affect available smooth muscle NO. Further experimental and theoretical studies are required to account for distribution of NOS isoforms and determine NO availability in vasculatures of different tissues.

model mathematical; model computational; nitric oxide; neuronal nitric oxide synthase; myoglobin; blood substitute; endothelial and neuronal nitric oxide synthase knockouts

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