Date of Graduation

5-2008

Document Type

Thesis

Degree Name

Bachelor of Science in Biological Engineering

Degree Level

Undergraduate

Department

Biological and Agricultural Engineering

Advisor

Kavdia, Mahendra

Reader

Costello, Thomas A.

Second Reader

Bajwa, Sreekala

Abstract

Nitric oxide (NO) is inactivated in the human body when exposed to superoxide (O2 -). This reaction forms peroxynitrite (ONOO-). Superoxide is produced in the cardiac system by several different ways, including NAD(P)H oxidase. Superoxide dismutase (SOD) breaks down superoxide into oxygen and hydrogen peroxide. This prevents superoxide from reacting with nitric oxide and allows normal function to take place. Superoxide and peroxynitrite are main contributors to vascular disease in the human body, in particular hypertension. Experiments have shown that there was an increase of superoxide production in spontaneously hypertensive rats (SHR) vs. age-matched Wistar Kyoto rats (WKY) that were normotensive. The increase in superoxide production intensified in the presence of scavenger DETCA Cu2+/Zn2+. A mathematical model has been developed by Kavdia and Popel to calculate concentrations of NO, ONOO-, and O2 - in the arterial and venule pair. Using this model we calculated the arterial and venule NO, ONOO-, and O2 - concentration profiles for normotension, hypertension, SOD inactivation, and NAD(P)H stimulated cases, and analyzed which specific regions showed amplification or reductions in concentrations. The inactivation of SOD allowed O2 - concentration to significantly increase by 10-fold under basal conditions in hypertensive mice, while reducing the NO concentration in the model. Basilar arteries from hypertensive rats showed an increase of 4.1-fold in Nox4 compared to normotensive rats. The results suggest that the increase in superoxide in hypertensive rats is in correlation with the increase of NAD(P)H oxidase in these rats. The trends in superoxide production in this paper can help understand hypertension and vascular disease more thoroughly. Further, the increase of Nox1 and Nox4 expression suggested, for future research, the specific regions where O2 - will be high and needs to be evaluated.

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