L-arginine limits myocardial cell death secondary to hypoxia-reoxygenation by a cGMP-dependent mechanism.
The objective of this study was to investigate the effect of L-arginine supplementation on myocardial cell death secondary to hypoxia-reoxygenation. Isolated rat hearts (n = 51) subjected to 40 min of hypoxia and 90 min of reoxygenation received 3 mM L-arginine and/or 1 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a selective inhibitor of soluble guanylyl cyclase) throughout the experiment or during the equilibration, hypoxia, or reoxygenation periods. The incorporation of L-[3H]arginine into myocytes during energy deprivation was investigated in isolated adult rat myocytes. The addition of L-arginine to the perfusate throughout the experiment resulted in higher cGMP release (P < 0.05), reduced lactate dehydrogenase release (P < 0.05), and increased pressure-rate product (P < 0.05) during reoxygenation. These effects were reproduced when L-arginine was added only during equilibration, but addition of L-arginine during hypoxia or reoxygenation had no effect. Addition of ODQ either throughout the experiment or only during reoxygenation reversed the beneficial effects of L-arginine. L-[3H]arginine was not significantly incorporated into isolated myocytes subjected to energy deprivation. We conclude that L-arginine supplementation protects the myocardium against reoxygenation injury by cGMP-mediated actions. To be effective during reoxygenation, L-arginine must be added before anoxia.
D000818:Animals; D001120:Arginine / Q000493:pharmacokinetics*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley