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Nitric Oxide Bioavailability Regulation by Hemoglobin

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abstract
Nitric Oxide (NO) is a diatomic molecule with one unpaired electron which makes it highly reactive. Because of its small size it can diffuse rapidly through body tissues. These characteristics allow NO to function very well as local signal transductor. NO plays an important role in the dilation of blood vessels. It is produced in the endothelial cells which line the inside of blood vessel walls. Smooth muscle tissue, which completely surrounds blood vessels, can tense (contract) or relax to decrease or increase the diameter of a blood vessel. Upon diffusion of NO to the smooth muscle cells, a reaction cascade is activated which eventually leads to smooth muscle relaxation and, hence, blood vessel dilation. Abnormally low levels of bioavailable NO may lead to an inability of smooth muscle to relax and to a subsequent increase in blood pressure, and cause other deleterious effects. Hemoglobin, the oxygen-carrying protein in blood, reacts rapidly with NO. Normally, however, hemoglobin is encapsulated within red blood cells. This limits its proximity to the endothelial cell layer, restricting its uptake rate of NO. Several diffusional barriers are potentially responsible for this rate limitation. The contribution of each of these barriers to the overall rate reduction, compared with free hemoglobin, is currently under investigation and is necessary to know in order to develop efficient blood substitutes of membrane-encapsulated hemoglobin. In addition, there is evidence that, under certain conditions, NO may be exported from within an erythrocyte to affect vasodilation. When hemoglobin escapes red blood cells its proximity to the endothelial cell layer is no longer restricted. This results in increased scavenging of NO by hemoglobin and in an impaired capacity of blood vessels to dilate. This occurs in hemolytic diseases as well as during transfusion of aged banked blood. The presented work determines the rate limiting factors of NO uptake by membrane-encapsulated hemoglobin under certain conditions, ways in which NO uptake by cell-free hemoglobin may be prevented, and investigates some possible mechanisms for NO export from within a red blood cell.
subject
Haptoglobin
Hemoglobin
Nitric Oxide
Nitrite
Red Blood Cells
Vasodilation
contributor
Azarov, Ivan Alekseyevich (author)
Kim-Shapiro, Daniel B (committee chair)
King, Bruce (committee member)
Bonin, Keith D (committee member)
Cho, Samuel (committee member)
Guthold, Martin (committee member)
date
2011-07-14T20:35:11Z (accessioned)
2013-07-14T08:30:09Z (available)
2011 (issued)
degree
Physics (discipline)
embargo
2013-07-14 (terms)
identifier
http://hdl.handle.net/10339/33431 (uri)
language
en (iso)
publisher
Wake Forest University
title
Nitric Oxide Bioavailability Regulation by Hemoglobin
type
Dissertation

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