Hydrogen-sulfide-mediated vasodilatory effect of nucleoside 5′-monophosphorothioates in perivascular adipose tissue
Hydrogen-sulfide-mediated vasodilatory effect of nucleoside 5′-monophosphorothioates in perivascular adipose tissue
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DOI：
10.1139/cjpp-2014-0543
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发表时间：
2015-07-01
影响因子：
2.1
通讯作者：
Halas, Krzysztof
中科院分区：
文献类型：
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作者：
Beltowski, Jerzy;Guranowski, Andrzej;Halas, Krzysztof
硫化氢（H2S）在血管周围脂肪组织（PVAT）中合成并诱导血管舒张。我们研究了含硫AMP和GMP类似物AMPS和GMPS是否可以在PVAT中充当H2S供体。用极谱传感器测定了离体大鼠主动脉周围脂肪组织（PAT）产生H2S的能力。此外，检测了苯肾上腺素诱导的有（+）或无（-）PAT的主动脉环收缩性。在P2 X（7）受体激动剂BzATP存在下，分离的PAT从AMPS或GMPS产生H2S。苯肾上腺素诱发的PAT（+）环收缩力低于PAT（-）环。AMPS或GMPS对PAT（-）环的收缩力无影响，但与BzATP联合使用时，在用炔丙基甘氨酸抑制内源性H_2S产生时，可降低PAT（+）环的收缩力。高脂饮食减少PAT的内源性H2S产生。有趣的是，AMPS和GMPS被肥胖大鼠的PAT转化为H2S，并且即使在没有BzATP的情况下，从这些动物分离的PAT（+）主动脉环的收缩性也降低。我们的结论是：（i）当P2 X（7）受体被激活时，AMPS和GMPS可被PAT水解为H2S;（ii）高脂饮食损害PAT产生的内源性H2S;（iii）在无P2 X（7）刺激的肥胖动物中，AMPS和GMPS可恢复PAT的抗收缩作用。
Hydrogen sulfide (H2S) is synthesized in perivascular adipose tissue (PVAT) and induces vasorelaxation. We examined whether the sulfur-containing AMP and GMP analogs AMPS and GMPS can serve as the H2S donors in PVAT. H2S production by isolated rat periaortic adipose tissue (PAT) was measured with a polarographic sensor. In addition, phenylephrine-induced contractility of aortic rings with (+) or without (-) PAT was examined. Isolated PAT produced H2S from AMPS or GMPS in the presence of the P2X(7) receptor agonist BzATP. Phenylephrine-induced contractility of PAT(+) rings was lower than of PAT(-) rings. AMPS or GMPS had no effect on the contractility of PAT(-) rings, but used together with BzATP reduced the contractility of PAT(+) rings when endogenous H2S production was inhibited with propargylglycine. A high-fat diet reduced endogenous H2S production by PAT. Interestingly, AMPS and GMPS were converted to H2S by PAT of obese rats, and reduced contractility of PAT(+) aortic rings isolated from these animals even in the absence of BzATP. We conclude that (i) AMPS and GMPS can be hydrolyzed to H2S by PAT when P2X(7) receptors are activated, (ii) a high-fat diet impairs endogenous H2S production by PAT, (iii) AMPS and GMPS restore the anticontractile effects of PAT in obese animals without P2X(7) stimulation.