title: Perivascular adipose tissue contains functional catecholamines.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: N
authors.initials: N
authors.lastname: Ayala-Lopez
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: M
authors.initials: M
authors.lastname: Martini
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: W F
authors.initials: WF
authors.lastname: Jackson
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: E
authors.initials: E
authors.lastname: Darios
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: R
authors.initials: R
authors.lastname: Burnett
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: B
authors.initials: B
authors.lastname: Seitz
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: G D
authors.initials: GD
authors.lastname: Fink
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
authors.forename: S W
authors.initials: SW
authors.lastname: Watts
keywords: blood pressure; catecholamines; indirect sympathomimetic; perivascular adipose tissue