Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells

Kejing Chen, Aleksander S Popel

Research output: Contribution to journalArticle

Abstract

Vascular endothelium expressing endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), which has a number of important physiological functions in the microvasculature. The rate of NO production by the endothelium is a critical determinant of NO distribution in the vascular wall. We have analyzed the biochemical pathways of NO synthesis and formulated a model to estimate NO production by the microvascular endothelium under physiological conditions. The model quantifies the NO produced by eNOS based on the kinetics of NO synthesis and the availability of eNOS and its intracellular substrates. The predicted NO production from microvessels was in the range of 0.005-0.1 μM/s. This range of predicted values is in agreement with some experimental values but is much lower than other rates previously measured or estimated from experimental data with the help of mathematical modeling. Paradoxical discrepancies between the model predictions and previously reported results based on experimental measurements of NO concentration in the vicinity of the arteriolar wall suggest that NO can also be released through eNOS-independent mechanisms, such as catalysis by neuronal NOS (nNOS). We also used our model to test the sensitivity of NO production to substrate availability, eNOS concentration, and potential rate-limiting factors. The results indicated that the predicted low level of NO production can be attributed primarily to a low expression of eNOS in the microvascular endothelial cells.

Original languageEnglish (US)
Pages (from-to)668-680
Number of pages13
JournalFree Radical Biology and Medicine
Volume41
Issue number4
DOIs
StatePublished - Aug 15 2006

Fingerprint

Endothelial cells
Nitric Oxide
Endothelial Cells
Nitric Oxide Synthase Type III
Microvessels
Endothelium
Availability
Vascular Endothelium
Substrates
Catalysis
Blood Vessels

Keywords

  • Computational model
  • Mathematical model
  • Nitric oxide synthase
  • Reaction kinetics
  • Theoretical model

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells. / Chen, Kejing; Popel, Aleksander S.

In: Free Radical Biology and Medicine, Vol. 41, No. 4, 15.08.2006, p. 668-680.

Research output: Contribution to journalArticle

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