We investigated the effects of in vivo treatment with the angiotensin-converting enzyme inhibitor (ACE-I) captopril and/or of in vitro administration of L-arginine on the metabolism and ischemia-reperfusion injury of the isolated perfused rat myocardium. Captopril (50 mg/l in drinking water, 4 weeks) raised the myocardial content of glycogen. After 25-min global ischemia, captopril treatment, compared with the controls, resulted in lower rates of lactate dehydrogenase release during reperfusion (8.58±1.12 vs. 13.39±1.88 U/heart/30 min, p<0.05), lower myocardial lactate contents (11.34±0.93 vs. 21.22±4.28 µmol/g d.w., p<0.05) and higher coronary flow recovery (by 25 %), and prevented the decrease of NO release into the perfusate during reperfusion. In control hearts L-arginine added to the perfusate (1 mmol/l) 10 min before ischemia had no effect on the parameters evaluated under our experimental conditions, presumably because of sufficient saturation of the myocardium with L-arginine. In the hearts of captopril-treated rats, L-arginine further increased NO production during reperfusion and the cGMP content before ischemia. Our results have shown that long-term captopril treatment increases the energy potential and has a beneficial effect on tolerance of the isolated heart to ischemia. L-arginine added into the perfusate potentiates the effect of captopril on the NO signaling pathway., J. Divišová, H. Vavřínková, M. Tutterová, L. Kazdová, E. Meschišvili., and Obsahuje bibliografii
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 ·FeS1 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., H. Vavřínková, M. Tutterová, P. Stopka, J. Divišová, L. Kazdová, Z. Drahota., and Obsahuje bibliografii