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Red blood cell derived vasodilators : determination and modulation

Title:

Red blood cell derived vasodilators : determination and modulation

Garcia, Juliana (2009) Red blood cell derived vasodilators : determination and modulation. Masters thesis, Concordia University.

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Abstract

A luciferin-luciferase chemiluminescence method was used to quantify extracellular adenosine triphosphate (ATP) released by red blood cells (RBCs) after stimulation with nitroglycerin, a potent vasodilatory drug. Attenuation in the amount of ATP released from RBCs was observed after treatment with increasing concentrations of nitroglycerin or nitrite. However, RBCs exposed to nitroglycerin or nitrite for < 5 min released increased amounts of ATP. A mechanism of blood flow regulation through an ATP-NO/NO 2 - pathway is proposed. Nitroglycerin-derived NO 2 - is converted within RBCs to NO, which might activate ATP release. In vivo, ATP will stimulate endothelial nitric oxide synthase (eNOS), increasing NO production and causing vasodilation. NO could diffuse into the blood stream where it is converted to NO 2 - and taken up by downstream RBCs, further increasing their ATP production. Thus, the original RBC-derived NO 2 - /NO signal could be amplified both by the action of ATP and NO. Nitroglycerin was also shown to act as a "suicide substrate" for RBC glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH reduced nitroglycerin to glyceryl dinitrates and NO 2 - using its active-site cysteines as electrons donors. This inactivation inhibited the bioconversion of nitroglycerin to NO 2 and caused an attenuation of the drug's effect. The dehydrogenase activity of GAPDH was also suppressed, thereby limiting the production of ATP and propagation of the vasodilation signal. The extracellular profile of ATP-derived ADP, AMP and adenosine was additionally studied by LC-UV. Preliminary ESI mass spectrometric analysis of epoxyeicosatrienoic acids and prostacyclin, RBC vasodilators derived from arachidonic acid, was explored.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Garcia, Juliana
Pagination:xviii, 124 leaves : ill. (some col.) ; 29 cm.
Institution:Concordia University
Degree Name:M. Sc.
Program:Chemistry
Date:2009
Thesis Supervisor(s):English, A. M
ID Code:976381
Deposited By: Concordia University Library
Deposited On:22 Jan 2013 16:24
Last Modified:18 Jan 2018 17:42
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