We examined the role of the nitric oxide (NO) pathway on ischemia-reperfusion injury with the use of isolated perfused guinea pig hearts. We administered to the heart either L-arginine or N-nitro-L-arginine methyl ester (L-NAME) before or after 20 min of ischemia, and we observed the heart rate, aortic pressure, and contractile force, as well as the levels of malondialdehyde (MDA) and glutathione (GSH). We observed that L-NAME increased the tissue MDA levels and aortic pressure. On the other hand, L-arginine before the onset of reperfusion decreased aortic pressure and tissue MDA levels but increased the tissue GSH levels. We concluded that L-arginine administration before the onset of reperfusion improves myocardial recovery from ischemic injury. (C) 2000 Elsevier Science Inc. All rights reserved.