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学科主题基础医学
Inhibition of Phosphoinositide 3-Kinase Potentiates Relaxation of Porcine Coronary Arteries Induced by Nitroglycerin by Decreasing Phosphodiesterase Type 5 Activity
Dou, Dou1,2; Guo, Yixuan1; Ying, Lei1; Liu, Juan1; Xu, Xiaojian1; Yu, Xiaoxing1; Gao, Yuansheng1,2
关键词Nitric oxide Smooth muscle Vasodilatation
刊名CIRCULATION JOURNAL
2012
DOI10.1253/circj.CJ-11-0802
76期:1页:230-237
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
资助者National Natural Science Foundation of China ; Ministry of Education for New Teachers ; Peking University Health Science Center Foundation for New Teachers ; National Natural Science Foundation of China ; Ministry of Education for New Teachers ; Peking University Health Science Center Foundation for New Teachers
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]DEPENDENT PROTEIN-KINASE ; SENSITIVE GUANYLYL CYCLASE ; SMOOTH-MUSCLE RELAXATION ; NITRIC-OXIDE ; CYCLIC-GMP ; CA2+ CHANNELS ; HYPERTENSIVE-RATS ; ENDOTHELIAL-CELLS ; NITRATE TOLERANCE ; PHOSPHORYLATION
英文摘要

Background: Vessel tension can be modulated by phosphoinositide 3-kinase (PI3K) acting on L-type calcium channel, rho kinase and phosphodiesterase (PDE) type 3 in smooth muscle cells. Inhibition of PI3K could increase the relaxation of porcine coronary arteries to nitroglycerin independent of this pathway, and the aim of the present study was therefore to determine the underlying mechanisms.

Methods and Results: Isolated porcine coronary arteries were dissected from the heart and cut into rings in ice-cold modified Krebs-Ringer bicarbonate buffer. The response of these vessels was studied by using the organ chamber technique; the content of cyclic guanosine monophosphate (cGMP) was determined by using enzyme-linked immunosorbent assay kit; and PI3K and Akt activity were determined by measuring the phosphorylation level of their downstream signaling molecule on Western blot. Inhibition of PI3K with 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran4-one hydrochloride (LY294002) potentiated the relaxation of porcine coronary arteries to nitroglycerin and nitric oxide (NO), but not to 8-bromo-guanosine 3′5′-cyclic monophosphate, isoproterenol or (R)-(+)-trans-4-(1-Aminoethyl)-N-(4-Pyridyl)cyclohexanecarboxamide dihydrochloride monohydrate (Y27632). Increased relaxation induced by LY294002 was eliminated by Akt1/2 kinase inhibitor (Akt-I: 1,3-dihydro-1-(1-((4-(6-phenyl-1H-imidazo(4,5-g)quinoxalin-7-yl)phenyl)methyl)-4-piperidinyl)-2H-benzimidazol-2-one trifluoroacetate salt hydrate) or zaprinast, but was not affected by 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, nifedipine or milrinone. Inhibition of Akt caused similar effects as LY294002. Incubation with LY294002 or Akt-I decreased the activity of PI3K and Akt but augmented the elevation of cGMP caused by NO. Enhanced cGMP elevation induced by LY294002 or Akt-I was also eliminated by zaprinast.

Conclusions: PI3K Akt signaling may affect vascular tone through a stimulatory effect on PDE type 5. (Circ J 2012; 76: 230-237)

语种英语
所属项目编号30870938 ; 81001433 ; 20100001120037 ; BMU20090510
资助者National Natural Science Foundation of China ; Ministry of Education for New Teachers ; Peking University Health Science Center Foundation for New Teachers ; National Natural Science Foundation of China ; Ministry of Education for New Teachers ; Peking University Health Science Center Foundation for New Teachers
WOS记录号WOS:000298771100037
引用统计
被引频次:8[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/400002259/66405
专题北京大学基础医学院_心血管所
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
2.Peking Univ, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Dou, Dou,Guo, Yixuan,Ying, Lei,et al. Inhibition of Phosphoinositide 3-Kinase Potentiates Relaxation of Porcine Coronary Arteries Induced by Nitroglycerin by Decreasing Phosphodiesterase Type 5 Activity[J]. CIRCULATION JOURNAL,2012,76(1):230-237.
APA Dou, Dou.,Guo, Yixuan.,Ying, Lei.,Liu, Juan.,Xu, Xiaojian.,...&Gao, Yuansheng.(2012).Inhibition of Phosphoinositide 3-Kinase Potentiates Relaxation of Porcine Coronary Arteries Induced by Nitroglycerin by Decreasing Phosphodiesterase Type 5 Activity.CIRCULATION JOURNAL,76(1),230-237.
MLA Dou, Dou,et al."Inhibition of Phosphoinositide 3-Kinase Potentiates Relaxation of Porcine Coronary Arteries Induced by Nitroglycerin by Decreasing Phosphodiesterase Type 5 Activity".CIRCULATION JOURNAL 76.1(2012):230-237.
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