Ayala-Lopez N, Martini M, Jackson W F, Darios E, Burnett R, Seitz B, Fink G D, Watts S W
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317.
Pharmacol Res Perspect. 2014 Jun 1;2(3):e00041. doi: 10.1002/prp2.41.
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.
交感神经系统及其神经递质效应器对血压控制的重要性毋庸置疑。我们有了一项新发现，即血管周围脂肪组织（PVAT）含有高浓度的儿茶酚胺。我们推测PVAT含有足够可释放的儿茶酚胺来影响血管功能。采用高效液相色谱法、等长收缩性测定、免疫组织化学、整体动物实验方法和药理学来验证这一假设。在正常大鼠胸主动脉和肠系膜上动脉中，间接拟交感神经药酪胺引起浓度依赖性收缩，该收缩依赖于PVAT的存在。酪胺刺激从这两种动脉分离出的PVAT释放去甲肾上腺素（NA）、多巴胺（DA）和色胺5-羟色胺（5-HT）。在这两种动脉中，酪胺诱导的浓度依赖性收缩向右移位并被去甲肾上腺素转运体抑制剂尼索西汀（1 μM）、囊泡单胺转运体丁苯那嗪（10 μM）减弱，被α肾上腺素能受体拮抗剂哌唑嗪（100 nM）消除。DA和5-HT转运体抑制剂并未改变酪胺诱导的、依赖PVAT的收缩。去除腹腔神经节作为肠系膜上动脉PVAT的儿茶酚胺神经元来源，并未显著降低最大收缩幅度，也未使对酪胺的浓度依赖性收缩发生移位。离体主动脉的电场刺激不受PVAT存在的影响。这些数据表明，独立于交感神经的PVAT成分能够以酪胺敏感的方式释放NA，从而导致动脉收缩。由于PVAT与动脉紧密相邻，这增加了PVAT儿茶酚胺对动脉功能进行局部调控的可能性。
