Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

May 1994

Abstract

The vascular endothelial cell (EC) plays an important role in regulating vascular tone and local blood flow by sensing chemical and mechanical stimuli on the vascular wall and releasing a host of vasoactive substances upon activations of endogenous or exogenous vasoactive substances. The central hypothesis is that local control of blood now and autoregulatory behavior in the microcirculation is distinctive at different levels of the vasculature and is dependent on the cellular activities of the EC and its interaction with the local environment. The in vivo as well as the ex vivo, flow-controlled preparations of the hamster cheek pouch were utilized. Inhibition of Endothelium-Derive Relaxing Factor (EDRF) synthesis and the functional impairment by light-dye (L-D) treatment were used to remove functional characteristics of the EC. It is found that the EC played differential roles in modulating vascular tone and blood flow in distinct segments of arterioles. Impairment of the EC by L-D treatment significantly reduced both acetylcholine (Ach)-induced dilation and the local angiotensin conversion in small (4th order) arterioles (A$\sb4$). Whereas, data obtained after inhibition of EDRF synthesis indicated that EDRF pathway appeared to be the dominant regulatory mechanism mediating agonists (e.g. Ach)-induced responses in these small vessels. In large (2nd order) arterioles (A$\sb2$), on the other hand, neither L-D treatment nor EDRF inhibition affected Ach-induced dilation or local angiotensin conversion; therefore, these responses seemed to be independent of the EC or EDRF pathway. Autoregulation was observed in both A$\sb2$ and A$\sb4$ when perfusion flow (shear stress) and perfusion pressure (stretch) were elevated. Nevertheless, the underlying regulatory mechanisms in response to mechanical stimuli differed in these series-arranged arterioles. The EC/EDRF-dependent, flow-induced dilation was dominant in A$\sb2$; whereas, the myogenic autoregulation (which appears to be independent of the EC) played major role in A$\sb4$. Therefore, the function of the EC does not appear homogenous throughout the arteriolar portion of the microcirculation. Thus, the local control of blood flow and autoregulatory behavior in the microcirculation is distinctive at different levels of the vasculature; whereas, the differential role of the EC in discrete segments of series-arranged arterioles seems to be the determinant for these differences. These differential modulations of vascular tone and blood flow by the EC at discrete levels of the microcirculation may have important implications in pathological conditions, such as hypertension, diabetes, and atherosclerosis.

Document Type

Dissertation - unrestricted

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