Date: Thursday, December 1, 2016
Perivascular adipose tissue (PVAT), fat that surrounds blood vessels, has an active role in regulating vascular tone. PVAT is important to blood vessel function in many respects by altering the proliferation, migration, and inflammation of vascular smooth muscle, in addition to the modulation of vascular tone through the release of vasoactive molecules. Arteries and veins respond to adrenergic activation followed by changes in blood pressure. Adipose tissue is a complex organ that contains within it cells that have adrenergic components. A comprehensive characterization of an adrenergic system within PVAT has not been performed. An adrenergic system in mesenteric PVAT may mechanistically connect obesity and hypertension. We hypothesized that PVAT can release, metabolize, and take up norepinephrine (NE) to constitute an adrenergic system. We investigated the adrenergic system in PVAT by analyzing PVAT gene expression and protein profiles, performing immunohistochemistry and transport imaging on adipocytes, measuring PVAT catecholamines by HPLC, and by performing functional contractility studies. The research covered in this dissertation will provide evidence that PVAT 1) contains a vasoactive source of NE, 2) inactivates NE action on the blood vessel by uptake through molecular transport and that 3) NE metabolism reduces contraction of mesenteric arteries to NE. These findings are an important contribution to the field of PVAT research because they directly connect PVAT to the modulation of blood vessel function through an adrenergic system and set the foundation for new hypotheses on how PVAT’s adrenergic system may function in diseases such as obesity and hypertension.