Date of Award

Spring 1998

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Biomedical Sciences

Committee Director

Frank Lattanzio

Committee Director

Russell L. Prewitt

Committee Member

Barbara Hargrave

Committee Member

Howard White

Abstract

The ability of cells to respond to mechanical stimuli has been studied through a variety of techniques in numerous cell types. The cells of the vascular wall have adapted to specific mechanical stresses through the activation of intracellular signaling pathways which result in cell-specific responses such as hypertrophy, hyperplasia, proliferation, and migration. Vascular smooth muscle of the arteries have been shown to be sensitive to mechanical stimuli such as stretch, and pressure.

This study attempts to add to the current knowledge of mechanotransduction by utilizing the isolated artery preparation. This preparation allows for the study of vascular smooth muscle signal transduction in response to physiologically relevant stimuli under controlled conditions. In this regard, this study will relate the ability of vascular smooth muscle to respond to normal and pathological increases in intraluminal pressure.

The data presented suggests that intraluminal pressure may activate discrete signaling pathways in isolated arteries. The activation of calcium entry through voltage-operated calcium channels appears obligatory for the myogenic response to increases in intraluminal pressure, and this pathway may interact with calcium sensitizing pathways involving phospholipase C. In contrast, the expression of the proto-oncogene, c-fos, in response to pathological increases in intraluminal pressure is regulated by tyrosine kinase pathways.

Comments

Dissertation submitted to the Faculty of Eastern Virginia Medical School and Old Dominion University in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biomedical Sciences.

DOI

10.25777/v3ab-1y39

ISBN

9780599059566

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