Disturbance of vasodilation via protease-activated receptor 2 in SHRSP.Z-Leprfa/IzmDmcr rats with metabolic syndrome
Disturbance of vasodilation via protease-activated receptor 2 in SHRSP.Z-Leprfa/IzmDmcr rats with metabolic syndrome
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DOI：
10.1016/j.vph.2014.06.005
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发表时间：
2014-10-01
影响因子：
4
通讯作者：
Shinozuka, Kazumasa
中科院分区：
文献类型：
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作者：
Kagota, Satomi;Maruyama, Kana;Shinozuka, Kazumasa
蛋白酶活化受体-2 （PAR2）激活可引起血管炎症和血管舒张，但其在代谢综合征（MetS）中的作用仍不确定。因此，我们检测了par2是否诱导了SHRSP的血管舒张。Z-Lepr(fa)/IzmDmcr大鼠（SHRSP.ZF）受损，如果是，给予替米沙坦是否具有保护作用。par2激活肽，2-呋喃酰- ligrlo -酰胺（2fly），放松Wistar-Kyoto大鼠（WKY）和SHRSP.ZF分离的肠系膜动脉上一级分支（MAs）。在SHRSP中，2个蝇类的Superior-MA松弛较少。ZF比WKY。在SHRSP中，一阶MAs被2fly的松弛是相同的。ZF和WKY。NO合成酶抑制剂部分减少了苍蝇诱导的SHRSP中一级和一级MAs的松弛。ZF和MY；SHRSP.ZF对松弛的抑制成比例地更大。在SHRSP。ZF、硝普苷诱导的松弛和可溶性鸟苷环化酶表达降低。在SHRSP。替米沙坦逆转了这些异常，降低了血压和血清中硫代巴比妥酸反应性物质（氧化应激指标）的水平。与大口径MAs相比，通过PAR2激活的血管舒张在小口径MAs中得以保留，即使MetS降低了no依赖性松弛机制。NO和非NO松弛因子有助于par2介导的MAs松弛，并且可能改变因子之间的平衡以保持MetS中的血管舒张。替米沙坦通过保护动脉免受氧化应激而预防MetS中的血管功能障碍。(C) 2014爱思唯尔公司版权所有。
Protease-activated receptor-2 (PAR2) activation causes vascular inflammation and vasodilation, but its role in metabolic syndrome (MetS) remains uncertain. Therefore, we examined whether the PAR2-induced vasodilation of SHRSP.Z-Lepr(fa)/IzmDmcr rats (SHRSP.ZF) is impaired and if so, whether administering telmisartan is protective.PAR2-activating peptide, 2-furoyl-LIGRLO-amide (2fly), relaxed the isolated superior and first-order branches of mesenteric arteries (MAs) from Wistar-Kyoto rats (WKY) and SHRSP.ZF. Superior-MA relaxation by 2fly was less in SHRSP.ZF than in WKY. Relaxation of first-order MAs by 2fly was the same in SHRSP.ZF and WKY. NO synthase inhibitor partially reduced 2fly-induced relaxation of superior and first-order MAs in SHRSP.ZF and MY; inhibition of relaxation was proportionately larger in SHRSP.ZF. In SHRSP.ZF, nitroprusside-induced relaxation and the expression of soluble guanylyl cyclase decreased. In SHRSP.ZF, telmisartan reversed these abnormalities, and decreased blood pressure and serum levels of thiobarbituric acid reactive substances, an index of oxidative stress. Vasodilation via PAR2 activation was preserved in small-caliber MAs, in contrast to large-caliber MAs, even when MetS reduced NO-dependent relaxation mechanisms. NO and non-NO relaxing factor(s) contributed to PAR2-mediated relaxation in MAs, and the balance between factors may be altered to preserve vasodilation in MetS. Telmisartan prevented vascular dysfunction in MetS by protecting arteries against oxidative stress. (C) 2014 Elsevier Inc. All rights reserved.