The effect of captopril on nitric oxide formation and on generation of radical forms of mitochondrial respiratory chain compounds in ischemic rat heart.
The increase of radical forms of mitochondrial respiratory chain compounds (MRCC) is an indicator of an increased risk of the formation of oxygen radicals. Using electron paramagnetic resonance (EPR), we found an increase of signals corresponding to ubisemichinone radical (.QH) and ironsulfur proteins radical forms (-FeS) of these respiratory chain compounds during ischemia in the isolated perfused rat heart (.QH increased from 1.51 to 3.08, .FeS1 from 1.14 to 2.65 arbitrary units). During the 5-min reperfusion, the signals returned to normoxic levels. In isolated mitochondria exposed to anoxia and reoxygenation the radical forms of .QH and FeS2 changed in a similar manner as in the intact heart. A combination of in vivo captopril treatment and in vitro L-arginine administration significantly decreased the levels of MRCC radicals in the isolated myocardium (.QH from 2.61 to 1.72 and .FeS, from 1.82 to 0.46 under normoxia; .QH from 4.35 to 2.66 and .FeS1 from 1.93 to 1.35 during ischemia). This decrease in MRCC radical forms was associated with increased NO levels in the perfusate, determined as NO2- / NO3-, as well as tissue NO levels determined using EPR as the dinitrosyl iron complex (DNIC). These results provide new information about the cardioprotective effects of ACE inhibitors and L-arginine.
Vavrínková
H
H
Institute for Clinical and Experimental Medicine, Czech Academy of Sciences, Prague. havv@medicon.cz
Tutterová
M
M
Stopka
P
P
Divisová
J
J
Kazdová
L
L
Drahota
Z
Z
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D003067:Coenzymes; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D005609:Free Radicals; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D003067:Coenzymes; D005609:Free Radicals; D007506:Iron-Sulfur Proteins; D014451:Ubiquinone; D009569:Nitric Oxide; D001120:Arginine; D002216:Captopril; C024989:coenzyme Q10; D010100:Oxygen