The sympathetic nervous system and its neurotransmitter effectors are undeniably important to blood pressure control. We made the novel discovery that perivascular adipose tissue (PVAT) contains significant concentrations of catecholamines. We hypothesized that PVAT contains sufficient releasable catecholamines to affect vascular function. HPLC, isometric contractility, immunohistochemistry, whole animal approaches and pharmacology were used to test this hypothesis. In normal rat thoracic aorta and superior mesenteric artery, the indirect sympathomimetic tyramine caused a concentration-dependent contraction that was dependent on the presence of PVAT. Tyramine stimulated release of NA, dopamine (DA) and the tryptamine serotonin (5-HT) from PVAT isolated from both arteries. In both arteries, tyramine-induced concentration-dependent contraction was rightward-shifted and reduced by the noradrenaline transporter inhibitor nisoxetine (1 μM), the vesicular monoamine transporter tetrabenazine (10 μM) and abolished by the α adrenoreceptor antagonist prazosin (100 nM). Inhibitors of the DA and 5-HT transporter did not alter tyramine-induced, PVAT-dependent contraction. Removal of the celiac ganglion as a neuronal source of catecholamines for superior mesenteric artery PVAT did not significantly reduce the maximum or shift the concentration dependent contraction to tyramine. Electrical field stimulation of the isolated aorta was not affected by the presence of PVAT. These data suggest that PVAT components that are independent of sympathetic nerves can release NA in a tyramine-sensitive manner to result in arterial contraction. Because PVAT is intimately apposed to the artery, this raises the possibility of local control of arterial function by PVAT catecholamines.

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Perivascular adipose tissue (PVAT) is under recognized for its importance in blood pressure regulation. Visceral adipocytes reportedly contain catecholamines. Adipocytes in PVAT are directly adjacent to the blood vessels they surround and therefore the production, release and/or reuptake of catecholamines may significantly affect vascular tone. We hypothesize that an adrenergic system is present in PVAT. Glyoxylic acid staining revealed the presence of catecholamines in the cytosol of mesenteric PVAT adipocytes. Dopamine (DA), norepinephrine (NE) and epinephrine were quantified by HPLC in rat aortic PVAT, brown fat, mesenteric PVAT and retroperitoneal fat with NE being the most abundant at concentrations of 731.9, 815.0, 668.7 and 73.2 ng/g from each tissue, respectively. Two key enzymes in catecholamine synthesis; tyrosine hydroxylase and dopamine β-hydroxylase, were located to PVAT adipocytes by immunohistochemistry. The norepinephrine transporter (NET) was detected on mesenteric PVAT adipocytes by confocal microscopy using ASP+ (2μM), a fluorescent NET substrate. Uptake of ASP+ was blocked by the NET specific inhibitor nisoxetine (10μM) (see figure). These data show that PVAT contains all of the elements of an adrenergic system and may contribute to vascular and adipose function in health and disease.