Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide
Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide
复制标题
DOI：
10.1038/sj.bjp.0707228
复制
发表时间：
2007-06-01
影响因子：
7.3
通讯作者：
Lee, R. M. K. W.
中科院分区：
文献类型：
--
作者：
Gao, Y-J;Lu, C.;Lee, R. M. K. W.
背景和目的：血管周围脂肪组织（PVAT）可减弱血管收缩，但其机制尚不清楚。实验方法：取Wistar大鼠主动脉环，制备PVAT和E均完整（PVAT+E+）、去除PVAT或E（PVAT-E+或PVAT+E-）或去除PVAT和E（PVAT-E-）的主动脉环，进行功能研究。关键结果：PVAT-E-对苯丙氨酸和5-HT的收缩作用最强，PVAT+E+最低，PVAT+E-或PVAT-E+居中。在生物测定实验中，将与PVAT+环（供体）一起孵育的沐浴液转移到PVAT环（受体）会诱导受体的松弛。这种舒张被E去除、NO合酶抑制、NO清除、高细胞外K+或钙依赖性K+通道（K-Ca）阻断所消除。该溶液刺激分离的内皮细胞和PVAT-E+环中的NO产生。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+环而非PVAT-环对苯丙酮酸的收缩，但超氧化物歧化酶和Tiron可降低收缩。在PVAT-E环中，H2 O2减弱苯肾上腺素诱导的收缩。这种作用被sGC抑制抵消。结论：PVAT通过两种不同的机制发挥其抗血管收缩作用：一种是抑制PVAT- E-环的收缩，另一种是抑制PVAT- E-环的收缩。（1）通过释放可转移的舒张因子，其通过NO释放和随后的KCa通道激活诱导内皮依赖性舒张，（2）通过涉及H2 O2和随后的sGC活化的内皮非依赖性机制。英国药理学杂志（2007）。
Background and purpose: 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.Experimental approach: 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.Key results: 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.Conclusion: 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 KCa channel activation, and ( 2) by an endothelium- independent mechanism involving H2O2 and subsequent activation of sGC. British Journal of Pharmacology ( 2007).