Effect of ACE inhibitor captopril and L-arginine on the metabolism and on ischemia-reperfusion injury of the isolated rat heart.
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 micromol/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.
Divisová
J
J
Institute for Clinical and Experimental Medicine, Prague, Czech Republic. jadi@medicon.cz
Vavrínková
H
H
Tutterová
M
M
Kazdová
L
L
Meschisvili
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D002216:Captopril; D006152:Cyclic GMP