Abstract 407: Tyramine Reveals a Functional Adrenergic System in Perivascular Adipose Tissue

Abstract

The sympathetic nervous system is undeniably important to blood pressure control. With the discovery of an adrenergic system in perivascular adipose tissue (PVAT) around both the aorta and mesenteric artery, we hypothesized that this system could promote contraction of the vessel around which it lives. Using isolated tissue bath and HPLC techniques, we examined the mechanism of contraction to the indirect sympathomimetic tyramine. Tyramine (100 nM - 1 mM) caused a concentration dependent contraction that was dependent on the presence of PVAT in normal rat thoracic aorta (figure, maximum tyramine contraction as a % initial phenylephrine contraction + PVAT = 47+/2, -PVAT = 11+/2), superior mesenteric artery (+ PVAT =64+/15 , -PVAT = 6+/2), and mesenteric resistance artery (+ PVAT =83+/17 , -PVAT = 3+/1). Tyramine stimulated release of NE, dopamine (DA) and serotonin (5-HT) from PVAT isolated from the superior mesenteric artery. In the thoracic aorta, tyramine induced contraction (Max = 61+/-13%) was rightward shifted and maximum contraction inhibited by the norepinephrine transporter inhibitor nisoxetine (1 uM =25+/-9%), vesicular monoamine transporter tetrabenazine (10 uM; 43+/-10%) and abolished by the alpha adrenergic receptor antagonist prazosin (100 nM). Removal of the celiac ganglion as a neuronal source of NE reduced PVAT content by ~38% and reduced maximum tyramine contraction by only ~22%. These data suggest that PVAT components that are independent of the formal SNS can release NE in a tyramine-sensitive manner. One of these components may be the adipocyte itself, a novel finding that has implications for control of vascular tone and local metabolic control.