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痉挛性缺血实验犬模型中心包内腺苷、肌苷和次黄嘌呤的浓度

Pericardial concentrations of adenosine, inosine and hypoxanthine in an experimental canine model of spastic ischaemia.

作者信息

Kékesi Violetta, Zima Endre, Barát Erzsébet, Huszár Eva, Nagy Andrea, Losonczi László, Merkely Béla, Horkay Ferenc, Juhász-Nagy Alexander

机构信息

Department of Cardiovascular Surgery, Semmelweis University, Városmajor u. 68., H-1122 Budapest, Hungary.

出版信息

Clin Sci (Lond). 2002 Aug;103 Suppl 48:198S-201S. doi: 10.1042/CS103S198S.

DOI:10.1042/CS103S198S
PMID:12193085
Abstract

It has been shown that the adenosine concentration in the pericardial fluid of the normal heart is higher by one order of magnitude than that of the venous plasma. A further increase in the pericardial adenosine concentration was also demonstrated in myocardial ischaemia or hypoxia. It was proposed that pericardial nucleoside levels may represent the interstitial concentrations of the adenine nucleosides. An experimental model was designed to determine the intrapericardial concentrations of adenosine, inosine and hypoxanthine during coronary spasm provoked by intracoronary administration of endothelin-1 (ET-1; 0.08+/-0.02 nmol/g of myocardial tissue). In the in situ dog heart (n=10), adenosine, inosine and hypoxanthine concentrations were determined by HPLC in fluid samples collected from the closed pericardial sac before and after ET-1 administration, and from the systemic arterial blood. Systemic blood pressure, heart rate and standard ECG were registered continuously. We found that the nucleoside concentrations in the infusate samples increased significantly during coronary spasm [adenosine, 1.49+/-0.44 compared with 0.37+/-0.07 microM (P<0.05); inosine, 27.43+/-11.51 compared with 0.47+/-0.11 microM (P<0.05); hypoxanthine, 21.17+/-6.49 compared with 4.91+/-1.24 microM (P<0.05)], while a significant decrease in blood pressure and an elevation in ECG ST segments were observed. The levels of the purine metabolites did not change in the systemic blood. The data indicate that changes in adenine nucleoside levels measured in pericardial infusate samples reflect activation of coronary metabolic adaptation in this model of spastic ischaemia, and that pericardial nucleoside levels may characterize alterations in interstitial adenine nucleoside concentrations.

摘要

研究表明,正常心脏心包液中的腺苷浓度比静脉血浆中的腺苷浓度高一个数量级。心肌缺血或缺氧时,心包腺苷浓度也会进一步升高。有人提出,心包核苷水平可能代表腺嘌呤核苷的间质浓度。设计了一个实验模型,以确定在冠状动脉内注射内皮素-1(ET-1;0.08±0.02 nmol/g心肌组织)诱发冠状动脉痉挛期间心包内腺苷、肌苷和次黄嘌呤的浓度。在原位犬心脏(n = 10)中,通过高效液相色谱法测定ET-1给药前后从封闭心包囊中采集的液体样本以及全身动脉血中的腺苷、肌苷和次黄嘌呤浓度。连续记录全身血压、心率和标准心电图。我们发现,在冠状动脉痉挛期间,注入液样本中的核苷浓度显著增加[腺苷,1.49±0.44 μM,而给药前为0.37±0.07 μM(P<0.05);肌苷,27.43±11.51 μM,而给药前为0.47±0.11 μM(P<0.05);次黄嘌呤,21.17±6.49 μM,而给药前为4.91±1.24 μM(P<0.05)],同时观察到血压显著下降和心电图ST段抬高。全身血液中嘌呤代谢产物的水平没有变化。数据表明,在心包注入液样本中测量的腺嘌呤核苷水平变化反映了这种痉挛性缺血模型中冠状动脉代谢适应的激活,并且心包核苷水平可能表征间质腺嘌呤核苷浓度的变化。

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Pericardial concentrations of adenosine, inosine and hypoxanthine in an experimental canine model of spastic ischaemia.痉挛性缺血实验犬模型中心包内腺苷、肌苷和次黄嘌呤的浓度
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引用本文的文献

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The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias.腺苷代谢物肌苷是腺苷A2A受体的功能性激动剂,具有独特的信号偏向性。
Cell Signal. 2016 Jun;28(6):552-60. doi: 10.1016/j.cellsig.2016.02.010. Epub 2016 Feb 19.
2
Inosine induces presynaptic inhibition of acetylcholine release by activation of A3 adenosine receptors at the mouse neuromuscular junction.肌苷通过激活小鼠神经肌肉接头处的 A3 腺苷受体诱导乙酰胆碱释放的突触前抑制。
Br J Pharmacol. 2013 Aug;169(8):1810-23. doi: 10.1111/bph.12262.