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Abstract：
Background: Perivascular adipose tissue (PVAT) can decrease vascular contraction to NE. We tested the hypothesis that metabolism and/or uptake of vasoactive amines by mesenteric PVAT (MPVAT) could affect NE-induced contraction of the mesenteric resistance arteries. Methods: Mesenteric resistance vessels (MRV) and MPVAT from male Sprague-Dawley rats were used. RT-PCR and Western blots were performed to detect amine metabolizing enzymes. The Amplex® Red Assay was used to quantify oxidase activity by detecting the oxidase reaction product H2O2 and the contribution of PVAT on the mesenteric arteries\' contraction to NE was measured by myography. Results: Semicarbazide sensitive amine oxidase (SSAO) and monoamine oxidase A (MAO-A) were detected in MRV and MPVAT by Western blot. Addition of the amine oxidase substrates tyramine or benzylamine (1 mM) resulted in higher amine oxidase activity in the MRV, MPVAT, MPVAT\'s adipocyte fraction (AF), and the stromal vascular fraction (SVF). Inhibiting SSAO with semicarbazide (1 mM) decreased amine oxidase activity in the MPVAT and AF. Benzylamine-driven, but not tyramine-driven, oxidase activity in the MRV was reduced by semicarbazide. By contrast, no reduction in oxidase activity in all sample types was observed with use of the monoamine oxidase inhibitors clorgyline (1 μM) or pargyline (1 μM). Inhibition of MAO-A/B or SSAO individually did not alter contraction to NE. However, inhibition of both MAO and SSAO increased the potency of NE at mesenteric arteries with PVAT. Addition of MAO and SSAO inhibitors along with the H2O2 scavenger catalase reduced PVAT\'s anti-contractile effect to NE. Inhibition of the norepinephrine transporter (NET) with nisoxetine also reduced PVAT\'s anti-contractile effect to NE. Conclusions: PVAT\'s uptake and metabolism of NE may contribute to the anti-contractile effect of PVAT. MPVAT and adipocytes within MPVAT are a source of SSAO.
摘要：
背景：血管周围脂肪组织（PVAT）可以减少血管向NE的收缩。我们测试了以下假设：肠系膜PVAT（MPVAT）对血管活性胺的代谢和/或摄取可能影响NE诱导的肠系膜阻力动脉收缩。方法：使用雄性Sprague-Dawley大鼠的肠系膜阻力血管（MRV）和MPVAT。进行RT-PCR和Western印迹以检测胺代谢酶。Amplex®Red测定法用于通过检测氧化酶反应产物H2O2来定量氧化酶活性，并通过肌电图测量PVAT对肠系膜动脉收缩至NE的贡献。结果：Westernblot检测到MRV和MPVAT中的氨基脲敏感胺氧化酶（SSAO）和单胺氧化酶A（MAO-A）。胺氧化酶底物酪胺或苄胺（1mM）的添加导致MRV中更高的胺氧化酶活性，MPVAT,MPVAT脂肪细胞分数（AF），和基质血管分数（SVF）。用氨基脲（1mM）抑制SSAO可降低MPVAT和AF中的胺氧化酶活性。苄胺驱动，但不是酪胺驱动的，氨基脲降低了MRV中的氧化酶活性。相比之下,使用单胺氧化酶抑制剂clorgyline（1μM）或pargyline（1μM），未观察到所有样品类型的氧化酶活性降低。单独抑制MAO-A/B或SSAO不会改变对NE的收缩。然而,MAO和SSAO的抑制增加了NE在PVAT肠系膜动脉的效力。添加MAO和SSAO抑制剂以及H2O2清除剂过氧化氢酶降低了PVAT对NE的抗收缩作用。用尼索西汀抑制去甲肾上腺素转运蛋白(NET)也降低了PVAT对NE的抗收缩作用。结论:PVAT对NE的摄取和代谢可能有助于PVAT的抗收缩作用。MPVAT和MPVAT内的脂肪细胞是SSAO的来源。
