IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries
Chen, Zhengju1; Zhang, Xu1,2; Ying, Lei3; Dou, Dou1,2; Li, Yanhui2,4; Bai, Yun1; Liu, Juan1; Liu, Limei1,2; Feng, Han1; Yu, Xiaoxing1; Leung, Susan Wai-Sum5; Vanhoutte, Paul M.5,6; Gao, Yuansheng1,2
关键词Soluble Guanylyl Cyclase Inosine 3 &Prime -cyclic Monophosphate 5 &Prime Hypoxic Vasoconstriction Endothelium
刊名AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
2014-08-01
DOI10.1152/ajpheart.00132.2014
307期:3页:H328-H336
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Physiology ; Peripheral Vascular Disease
研究领域[WOS]Cardiovascular System & Cardiology ; Physiology
关键词[WOS]INOSINE TRIPHOSPHATE PYROPHOSPHATASE ; NUCLEOTIDYL CYCLASE ACTIVITY ; SOLUBLE GUANYLYL CYCLASE ; SMOOTH-MUSCLE-CELLS ; ENDOTHELIUM ; KINASES ; RELAXATION ; ACTIVATION ; ANOXIA ; OXYGEN
英文摘要

cGMP is considered the only mediator synthesized by soluble guanylyl cyclase (sGC) in response to nitric oxide (NO). However, purified sGC can synthesize several other cyclic nucleotides, including inosine 3′,5′-cyclic monophosphate (cIMP). The present study was designed to determine the role of cIMP in hypoxic contractions of isolated porcine coronary arteries. Vascular responses were examined by measuring isometric tension. Cyclic nucleotides were assayed by HPLC tandem mass spectroscopy. Rho kinase (ROCK) activity was determined by measuring the phosphorylation of myosin phosphatase target subunit 1 using Western blot analysis and an ELISA kit. The level of cIMP, but not that of cGMP, was elevated by hypoxia in arteries with, but not in those without, endothelium [except if treated with diethylenetriamine (DETA) NONOate]; the increases in cIMP were inhibited by the sGC inhibitor 1H-[1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Hypoxia (PO2: 25-30 mmHg) augmented contractions of arteries with and without endothelium if treated with DETA NONOate; these hypoxic contractions were blocked by ODQ. In arteries without endothelium, hypoxic augmentation of contraction was also obtained with exogenous cIMP. In arteries with endothelium, hypoxic augmentation of contraction was further enhanced by inosine 5′-triphosphate, the precursor for cIMP. The augmentation of contraction caused by hypoxia or cIMP was accompanied by increased phosphorylation of myosin phosphatase target subunit 1 at Thr(853), which was prevented by the ROCK inhibitor Y-27632. ROCK activity in the supernatant of isolated arteries was stimulated by cIMP in a concentration-dependent fashion. These results demonstrate that cIMP synthesized by sGC is the likely mediator of hypoxic augmentation of coronary vasoconstriction, in part by activating ROCK.

语种英语
WOS记录号WOS:000341080300007
项目编号81270341 ; 81373404 ; LQ13H020006 ; 777507M
资助机构National Natural Science Foundation of China ; Zhejiang Provincial Natural Science Foundation of China ; Hong Kong Research Grant Council (University of Hong Kong)
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55578
专题北京大学基础医学院_心血管所
北京大学基础医学院
北京大学第一临床医学院_急诊科
作者单位1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
3.Wenzhou Med Univ, Dept Pathophysiol, Wenzhou, Zhejiang, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
5.Univ Hong Kong, Dept Pharmacol & Pharm, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China
6.Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China
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GB/T 7714
Chen, Zhengju,Zhang, Xu,Ying, Lei,et al. cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries[J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY,2014,307(3):H328-H336.
APA Chen, Zhengju.,Zhang, Xu.,Ying, Lei.,Dou, Dou.,Li, Yanhui.,...&Gao, Yuansheng.(2014).cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries.AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY,307(3),H328-H336.
MLA Chen, Zhengju,et al."cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries".AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 307.3(2014):H328-H336.
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