Liu Huixia, Li Yanjing, An Yuanming, He Peixin, Wu Liling, Gao Yuansheng, Dou Dou
Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, China; Department of Physiology, Heze Medical College, Heze, Shandong, China.
Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, China.
Stem Cells Int. 2016;2016:2916017. doi: 10.1155/2016/2916017. Epub 2015 Dec 29.
Objective. Hypoxia-induced sustained contraction of porcine coronary artery is endothelium-independent and mediated by PI3K/Akt/Rho kinase. Nitroglycerin (NTG) is a vasodilator used to treat angina pectoris and acute heart failure. The present study was to determine the role of NTG in hypoxia-induced endothelium-independent contraction and the underlying mechanism. Methods and Results. Organ chamber technique was used to measure the isometric vessel tension of isolated porcine coronary arteries. Protein levels of phosphorylated and total Akt were determined by western blot. A sustained contraction of porcine coronary arteries induced by hypoxia was significantly reduced by NTG but not by isoproterenol. This contraction was also inhibited by DETA NONOate, 8-Br-cGMP, which can be reversed by ODQ, and Rp-8-Br-PET-cGMPS. The restored contraction was blocked by LY294002. The reduction of Akt-p at Ser-473 by NTG, DETA NONOate, and 8-Br-cGMP was significantly inhibited by ODQ, PKG-I. The decrease in Akt-p level by NTG and 8-Br-cGMP was prevented by calyculin A but not by okadaic acid. Conclusions. These results demonstrated that the endothelium-independent sustained hypoxic vasoconstriction can be prevented by NTG and that the inhibition of PI3K/Akt signaling pathway may be involved.
目的。缺氧诱导的猪冠状动脉持续收缩不依赖于内皮，由PI3K/Akt/ Rho激酶介导。硝酸甘油（NTG）是一种用于治疗心绞痛和急性心力衰竭的血管扩张剂。本研究旨在确定NTG在缺氧诱导的不依赖于内皮的收缩中的作用及其潜在机制。方法与结果。采用器官浴槽技术测量离体猪冠状动脉的等长血管张力。通过蛋白质免疫印迹法测定磷酸化Akt和总Akt的蛋白水平。NTG可显著减轻缺氧诱导的猪冠状动脉持续收缩，而异丙肾上腺素则无此作用。这种收缩也受到DETA NONOate、8-Br-cGMP的抑制，ODQ可逆转这种抑制作用，Rp-8-Br-PET-cGMPS也有此作用。LY294002可阻断恢复后的收缩。ODQ、PKG-I可显著抑制NTG、DETA NONOate和8-Br-cGMP对Ser-473位点Akt-p的降低作用。Calyculin A可阻止NTG和8-Br-cGMP引起的Akt-p水平降低，而冈田酸则无此作用。结论。这些结果表明，NTG可预防不依赖于内皮的持续性缺氧性血管收缩，且可能涉及PI3K/Akt信号通路的抑制。
