Protective Effect of Histidine on Hydroxyl Radical Generation Induced by Potassium-Depolarization in Rat Myocardium

We investigated the efficacy of histidine on potassium-depolarization induced hydroxyl radical (*OH) generation in the extracellular fluid of rat myocardium by a flexibly mounted microdialysis technique (O system). After the rat was anesthetized, a microdialysis probe was implanted in the left ventricular myocardium, and then sodium salicylate in Ringer's solution (0.5 nmol/microl per minute) was infused to detect the generation of *OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA). Infusion of KCl (70 mM) clearly produced an increase in *OH formation. However, when KCl in the presence of a high concentration of histidine (25 mM) was infused through the microdialysis probe, KCl failed to increase the 2,3-DHBA formation. To examine the effect of histidine on ischemia-reperfusion of the myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, a marked elevation of the levels of 2,3-DHBA was observed in the heart dialysate. However, when corresponding experiments were performed with histidine (25 mM)-pretreated animals, histidine prevented the ischemia-reperfusion induced *OH formation trapped as 2,3-DHBA. These results indicate that histidine may protect against K+-depolarization-evoked *OH generation in rat myocardium.