Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Medical Biophysics

Supervisor

McGuire, John J.

Abstract

Ageing, and type 2 diabetes are associated with cardiovascular diseases and endothelial dysfunction. Endothelial dysfunction is characterized by a decline in endothelium-mediated vasodilation. In this thesis, we determined the vascular function of hindlimb arteries supplying skeletal muscle and extremities using isolated arteries and wire myography. For ageing studies, we used Sprague Dawley rats and for type 2 diabetes we used the Zucker Diabetic Sprague Dawley strain. Vasodilation of hindlimb arteries with acetylcholine were impaired in both models. However, protease-activated receptor 2 mediated vasodilation was upregulated in arteries. Evidence of non-nitric oxide mechanisms were also found in peripheral vasculature. These data suggest heterogenous mechanisms of endothelium-mediated vasodilation in hindlimb vasculature which differ between models of endothelial dysfunction.

Summary for Lay Audience

The endothelium is a layer of cells that line the inside of our blood vessels and produces vasoactive compounds, that regulate the diameter of the vessels and blood flow. With ageing or diseases like type 2 diabetes, the endothelium undergoes a state of “endothelial dysfunction” which is characterized by a change in the production or response to vasoactive compounds. Endothelial dysfunction has been well-characterized in large arteries but has yet to be characterized in smaller blood vessels that feed the skeletal muscles of the leg or the feet. The first part of our study measured tension produced by live blood vessels in response to different drugs from old and young rats. The second part of our study compared the tension produced from blood vessels in healthy compared to a type 2 diabetic rats. This is the first study to employ the use of a new animal model of type 2 diabetes using this technique. We found that certain areas of the leg exhibit a lower magnitude of response to dilation inducing compounds. This warrants consideration in future studies on endothelial dysfunction in the hindlimb and could be beneficial to therapy development in the future.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Sunday, December 31, 2023

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