Background: The mechanism of the perivascular adipose tissue (PVAT) anticontractile effect is well characterized in rodent visceral vascular beds; however, little is known about the mechanism of PVAT anticontractile function in subcutaneous vessels. In addition, we have previously shown that PVAT anticontractile function is nitric oxide synthase (NOS) dependent but have not investigated the roles of NOS isoforms. Objective: Here, we examined PVAT anticontractile function in the mouse gracilis artery, a subcutaneous fat depot, in lean control and obese mice and investigated the mechanism in comparison to a visceral depot. Method: Using the wire myograph, we generated responses to noradrenaline and electrical field stimulation in the presence of pharmacological tools targeting components of the known PVAT anticontractile mechanism. In addition, we performed ex vivo “fat transplants” in the organ bath. Results: The mechanism of PVAT anticontractile function is similar between subcutaneous and visceral PVAT depots. Both endothelial and neuronal NOS isoforms mediated the PVAT anticontractile effect. Loss of PVAT anticontractile function in obesity is independent of impaired vasoreactivity, and function can be restored in visceral PVAT by NOS activation. Conclusions: Targeting NOS isoforms may be useful in restoring PVAT anticontractile function in obesity, ameliorating increased vascular tone, and disease.
J Vasc Res

中文翻译：

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血管周围脂肪组织的抗收缩功能由内皮细胞和神经元一氧化氮合酶亚型介导

背景：血管周围脂肪组织 (PVAT) 抗收缩作用的机制在啮齿动物内脏血管床中得到了很好的表征；然而，关于PVAT在皮下血管中抗收缩功能的机制知之甚少。此外，我们之前已经表明，PVAT 抗收缩功能依赖于一氧化氮合酶 (NOS)，但尚未研究 NOS 亚型的作用。目的：在这里，我们检查了小鼠股薄动脉（皮下脂肪库）、瘦对照和肥胖小鼠的 PVAT 抗收缩功能，并与内脏脂肪库相比研究了其机制。方法：使用线 myograph，我们在针对已知 PVAT 抗收缩机制的组件的药理学工具存在的情况下产生了对去甲肾上腺素和电场刺激的反应。此外，我们在器官浴中进行了离体“脂肪移植”。结果： PVAT 抗收缩功能的机制在皮下和内脏 PVAT 储库之间是相似的。内皮细胞和神经元 NOS 亚型均介导 PVAT 抗收缩作用。肥胖患者 PVAT 抗收缩功能的丧失与血管反应性受损无关，并且可以通过激活 NOS 恢复内脏 PVAT 的功能。结论：靶向 NOS 亚型可能有助于恢复肥胖患者的 PVAT 抗收缩功能，改善血管张力增加和疾病。
J Vasc Res