2-MERCAPTOPROPIONYLGLYCINE IMPROVES AORTIC FLOW AFTER REOXYGENATION IN WORKING RAT HEARTS

被引:29
作者
ZIMMER, G [1 ]
EVERS, J [1 ]
机构
[1] UNIV FRANKFURT, GUSTAV EMBDEN ZENT BIOL CHEM, THEODOR STERN KAI 7, D-6000 FRANKFURT, FED REP GER
关键词
D O I
10.1007/BF02005830
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The cardioprotective concentration range of the thiol drug 2-mercaptopropionylglycine (MPG) was investigated during reoxygenation after 30 min of hypoxia. It was found that aortic flow and frequency were increased by 1 mM MPG. Coronary flow, systolic and diastolic pressure were not significantly influenced by the drug. Mitochondria, isolated from hearts after termination of the perfusion phases, revealed increased values of RCI, when MPG had been present in the previous reoxygenation phase at 1 mM concentration. 5 mM MPG no longer showed a protective influence on the above cardiac and mitochondrial parmaters. ATPase activities were decreased at 1 mM MPG by 14% and at 5 mM MPG by 40% of the controls. The latter concentration of MPG also doubled the inhibitory action of carboxyatractyloside on ATPase activity, indicating a structural change of the adenine nucleotide carrier. 1 mM MPG is considered an optimal therapeutic range in this model. The mechanism of action most probably includes an SH/-S-S-interchange reaction as well as a free radical scavening mechanism. For many thiols, the latter is known to occur in the presence of metal ions.
引用
收藏
页码:445 / 451
页数:7
相关论文
共 40 条
[1]  
BEYERSDORF F, 1987, ARZNEIMITTELFORSCH, V37-1, P142
[2]  
BEYERSDORF F, 1985, MOL PHYSIOL, V8, P655
[3]   SIMPLE AND RAPID ASSAY OF OXIDATIVE PHOSPHORYLATION [J].
CHANCE, B ;
WILLIAMS, GR .
NATURE, 1955, 175 (4469) :1120-1121
[4]   OXIDATIVE-PHOSPHORYLATION RATE - INDEX FOR EVALUATION OF MITOCHONDRIAL-FUNCTION IN MYOCARDIAL ISCHEMIA [J].
EDOUTE, Y ;
KOTZE, JCN ;
LOCHNER, A .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1979, 11 (08) :831-833
[5]  
Estabrook R.W., 1974, METHODS ENZYMOLOGY, V10, P41, DOI [10.1016/0076-6879(67)10010-4, DOI 10.1016/0076-6879(67)10010-4]
[6]   OXYGEN-MEDIATED MYOCARDIAL DAMAGE DURING ISCHEMIA AND REPERFUSION - ROLE OF THE CELLULAR DEFENSES AGAINST OXYGEN-TOXICITY [J].
FERRARI, R ;
CECONI, C ;
CURELLO, S ;
GUARNIERI, C ;
CALDARERA, CM ;
ALBERTINI, A ;
VISIOLI, O .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1985, 17 (10) :937-945
[7]  
Fleischer S, 1979, Methods Enzymol, V55, P28
[8]  
FREISLEBEN HJ, 1988, IN PRESS ARCH BIOCH
[9]   A MULTIPARAMETER ANALYSIS OF THE PERFUSED RAT-HEART - RESPONSES TO ISCHEMIA, UNCOUPLERS AND DRUGS [J].
FUCHS, J ;
ZIMMER, G ;
BEREITERHAHN, J .
CELL BIOCHEMISTRY AND FUNCTION, 1987, 5 (04) :245-253
[10]   P-31-NMR SPECTROSCOPIC INVESTIGATIONS AND MITOCHONDRIAL STUDIES ON THE CARDIOPROTECTIVE EFFICIENCY OF 2-MERCAPTOPROPIONYLGLYCINE [J].
FUCHS, J ;
ZIMMER, G .
BIOCHEMICAL PHARMACOLOGY, 1986, 35 (24) :4381-4385