Gao Y-J, Lu C, Su L-Y, Sharma A M, Lee R M K W
Department of Anesthesia, Smooth Muscle Research Program, McMaster University, Hamilton, Ontario, Canada.
Br J Pharmacol. 2007 Jun;151(3):323-31. doi: 10.1038/sj.bjp.0707228. Epub 2007 Mar 26.
Perivascular adipose tissue (PVAT) attenuates vascular contraction, but the mechanisms remain largely unknown. The possible involvement of endothelium (E) and hydrogen peroxide (H2O2) was investigated.
Aortic rings from Wistar rats were prepared with both PVAT and E intact (PVAT+ E+), with either PVAT or E removed (PVAT- E+, or PVAT+ E-), or with both removed (PVAT- E-) for functional studies. Nitric oxide (NO) production was measured.
Contraction to phenylephrine and 5-HT respectively was highest in PVAT- E-, lowest in PVAT+ E+, and intermediate in PVAT+ E- or PVAT- E+. In bioassay experiments, transferring bathing solution incubated with a PVAT+ ring (donor) to a PVAT- ring (recipient) induced relaxation in the recipient. This relaxation was abolished by E removal, NO synthase inhibition, scavenging of NO, high extracellular K+, or blockade of calcium-dependent K+ channels (K(Ca)). The solution stimulated NO production in isolated endothelial cells and in PVAT- E+ rings. In E- rings, the contraction to phenylephrine of PVAT+ rings but not PVAT- rings was enhanced by catalase or soluble guanylyl cyclase (sGC) inhibitor, but reduced by superoxide dismutase and tiron. In PVAT- E- rings, H2O2 attenuated phenylephrine-induced contraction. This effect was counteracted by sGC inhibition. NO donor and H2O2 exhibited additive inhibition of the contraction to phenylephrine in PVAT- E- rings.
PVAT exerts its anti-contractile effects through two distinct mechanisms: (1) by releasing a transferable relaxing factor which induces endothelium-dependent relaxation through NO release and subsequent K(Ca) channel activation, and (2) by an endothelium-independent mechanism involving H2O2 and subsequent activation of sGC.
血管周围脂肪组织（PVAT）可减弱血管收缩，但其机制尚不清楚。本研究探讨了内皮细胞（E）和过氧化氢（H2O2）可能发挥的作用。
制备Wistar大鼠主动脉环，分别保留PVAT和E完整（PVAT+E+）、去除PVAT或E（PVAT-E+或PVAT+E-）、两者均去除（PVAT-E-），用于功能研究。检测一氧化氮（NO）生成量。
对去氧肾上腺素和5-羟色胺的收缩反应在PVAT-E-组中最高，在PVAT+E+组中最低，在PVAT+E-或PVAT-E+组中居中。在生物测定实验中，将与PVAT+环（供体）孵育的浴液转移至PVAT-环（受体）可诱导受体舒张。去除E、抑制NO合酶、清除NO、高细胞外钾或阻断钙依赖性钾通道（KCa）可消除这种舒张作用。该溶液可刺激分离的内皮细胞和PVAT-E+环产生NO。在E-环中，过氧化氢酶或可溶性鸟苷酸环化酶（sGC）抑制剂可增强PVAT+环对去氧肾上腺素的收缩反应，但对PVAT-环无此作用，而超氧化物歧化酶和替诺则可减弱该反应。在PVAT-E-环中，H2O2可减弱去氧肾上腺素诱导的收缩。sGC抑制可抵消该作用。NO供体和H2O2对PVAT-E-环中去氧肾上腺素诱导的收缩具有相加抑制作用。
PVAT通过两种不同机制发挥其抗收缩作用：（1）释放一种可转移的舒张因子，通过释放NO并随后激活KCa通道诱导内皮依赖性舒张；（2）通过一种不依赖内皮的机制，涉及H2O2并随后激活sGC。
