Date of Award

Spring 2006

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Rathore, Rajendra

Second Advisor

Kincaid, James R.

Third Advisor

Donaldson, William A.

Abstract

Nitric Oxide as a Biological Messenger. The Nobel Prize in Medicine in year 1998 was awarded to Murad, Furchgott, and Ignarro for the discovery of the signaling properties of nitric oxide - a small diatomic radical. The flurry of activities made in last two decades showed that NO could be synthesized by mammalian cells and could act as a physiological messenger as well as a cytotoxic agent and thus has increased the importance of its detection. For example, (i) The endothelium (inner lining) of blood vessels use nitric oxide (synthesized by endothelial NO synthase "eNOS") to signal the surrounding smooth muscles to relax and thus dilate the arteries which allow increase in blood flow. The nitroglycerin, amyl nitrate and other nitrate derivatives that are used in the treatment of heart diseases, such as angina, are now believed to function by release of NO from these nitrated material that reduce myocardial wall tension and are also believed to reduce arteriolar resistance that in turn decrease myocardial oxygen demand. (ii) Macrophages are types of cells in the immune system that produce nitric oxide by the aid of inducible nitric oxide synthase (iNOS) to kill invading bacteria.5 Under certain conditions, the uncontrolled release of nitric oxide in these cells can prove to be highly undesirable...

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