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Perivascular adipose tissue contains functional catecholamines - PubMed

  • ️Wed Jan 01 2014

Perivascular adipose tissue contains functional catecholamines

N Ayala-Lopez et al. Pharmacol Res Perspect. 2014.

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.

Keywords: blood pressure; catecholamines; indirect sympathomimetic; perivascular adipose tissue.

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Figures

Figure 1
Figure 1

(A) HPLC measures of catecholamine content (ng g tissue−1) in aortic PVAT, brown fat pad (interscapular), mesenteric PVAT, and retroperitoneal fat from the same rats. Bars represent mean ± SEM for number of animals in parentheses. (B) Representative image of glyoxylic acid staining of rat mesenteric PVAT where the left hand side is bright field picture, right hand side fluorescent glyoxylic acid image. Representative of four number of animals. (C) Detection of NA in the superior mesenteric PVAT. Representative of four individual animals. Left panel are images from sections exposed with primary antibody (primary), right images from sections not exposed to primary antibody (no primary). Arrows point regions of interest.

Figure 2
Figure 2

Tyramine-released catecholamines from mesenteric (A) and aortic (B) PVAT as measured through HPLC. Bars represent mean ± SEM for number of animals in parentheses. Solid bars are values for samples incubated with normal PSS, gray bars for samples incubated with 10−4 mol/L Tyramine.*Statistically significant increase (P < 0.05) versus appropriate control.

Figure 3
Figure 3

Tyramine-induced contraction in the isolated RA (A) and RMA (B) of the normal Sprague-Dawley rat. Points represent mean ± SEM for the number of animals in parentheses. Values in key legend are the response in milligrams to 10−5 mol/L PE.

Figure 4
Figure 4

(A) Left: Inhibition of tyramine-induced maximum contraction by the α1 adrenoceptor antagonist prazosin (1 μmol/L). Right: Quantification of inhibition of tyramine-induced contraction by a 10-fold lower concentration of prazosin. Bars represent mean ± SEM for number of animals in parentheses.*Significant difference versus appropriate control values (P < 0.05). (B) Contraction of isolated RA and RMA +/−PVAT to maximum electrical field stimulation (20 Hz). (C) NA content in artery proper and PVAT around artery for the RA and RMA. Bars represent mean ± SEM for number of animals in parentheses.*Statistically significant increase (P < 0.05) versus +PVAT values.

Figure 5
Figure 5

(A) Quantitation of RMA PVAT catecholamines in animals with a sham (black; SGx) or (white; CGx) celiac ganglionectomy. (B) Tyramine-induced RMA + PVAT contraction in animals with SGx or CGx surgery. (C) HPLC validation of CGX through reduced NA content of those tissues known to be innervated by the celiac ganglion (liver, small intestine and spleen). Bars represent mean ± SEM for number of animals in parentheses. *Statistically significant increase (P < 0.05) versus SGx values.

Figure 6
Figure 6

(A) Tyramine-induced contraction in the RA +PVAT in the presence of a series of inhibitors compared to water-based vehicle. (B) Tyramine-induced contraction in the RA + PVAT in the presence of the VMAT inhibitor tetrabenazine or DMSO vehicle. Points represent mean ± SEM for the number of animals in parentheses.

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