Responsiveness of rat aorta and pulmonary artery to cGMP generators in the presence of thiol or heme oxidant.
Responsiveness of rat aorta and pulmonary artery to cGMP generators in the presence of thiol or heme oxidant.
复制标题
在硫醇或血红素氧化剂存在下，大鼠主动脉和肺动脉对 cGMP 发生器的反应性。
DOI：
10.1016/j.jphs.2019.04.002
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发表时间：
2019
影响因子：
3.5
通讯作者：
Takaharu Ishibashi
中科院分区：
文献类型：
--
作者：
Masashi Tawa;Yuka Yamashita;Takayoshi Masuoka;Katsuya Nakano;Junko Yoshida;Matomo Nishio;Takaharu Ishibashi
本研究采用器官室法研究了巯基和血红素氧化剂对大鼠离体主动脉和肺动脉对cGMP发生器反应性的影响。一氧化氮（NO）供体硝普钠（SNP）诱导的舒张受损暴露于硫醇氧化剂二酰胺在主动脉和肺动脉，而可溶性鸟苷酸环化酶（sGC）刺激剂BAY 41-2272-或sGC激活剂BAY 60-2770诱导的舒张不受影响。巯基还原剂二硫苏糖醇后处理，SNP诱导的主动脉和肺动脉舒张的二酰胺损伤完全恢复。然而，无论血管类型如何，对SNP或BAY 41-2272的舒张反应因暴露于血红素氧化剂ODQ而受损，而对BAY 60-2770的反应增强。用血红素还原剂连二亚硫酸盐后处理可部分逆转ODQ诱导的效应。这些发现表明，硫醇氧化仅减弱血管对NO供体的反应性，血红素氧化减弱对NO供体和sGC刺激剂的反应性，但增强对sGC激活剂的反应性。因此，在氧化应激下，血管扩张剂的可用性顺序为：NO供体< sGC刺激剂< sGC激活剂。
This study investigated the effects of thiol and heme oxidants on responsiveness to cGMP generators in isolated rat aorta and pulmonary artery using an organ chamber. The nitric oxide (NO) donor sodium nitroprusside (SNP)-induced relaxation was impaired by exposure to the thiol oxidant diamide in both the aorta and the pulmonary artery, whereas the soluble guanylate cyclase (sGC) stimulator BAY 41-2272- or the sGC activator BAY 60-2770-induced relaxation was not affected. The impairment by diamide of SNP-induced aortic and pulmonary arterial relaxation was completely restored by post-treatment with the thiol reductant dithiothreitol. However, regardless of the vessel type, the relaxant response to SNP or BAY 41-2272 was impaired by exposure to the heme oxidant ODQ, whereas the response to BAY 60-2770 was enhanced. The ODQ-induced effects were reversed partially by post-treatment with the heme reductant dithionite. These findings indicate that thiol oxidation attenuates only the vascular responsiveness to NO donors and that heme oxidation attenuates the responsiveness to NO donors and sGC stimulators but augments that to sGC activators. Therefore, under oxidative stress, the order of usability of the vasodilators is suggested to be: NO donors < sGC stimulators < sGC activators.