Jpn. J. Pharmacol. 80 (3), 217-222 (1999)

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

Toshio Obata (1), Masahiro Aomine (2) and Yasumitsu Yamanaka (1)

(1) Department of Pharmacology, Oita Medical University, Hasama-machi, Oita 879-5593, Japan
(2) Division of Nutritional Physiology, Graduate School of Nutrition Science, Nakamura Gakuen University, Jonan-ku, Fukuoka 814-0198, Japan

Abstract: We investigated the efficacy of histidine on potassium-depolarization induced hydroxyI 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/microliter per minute) was infused to detect the generation of ・OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA). Infusion of KCI (70 mM) clearly produced an increase in ・OH formation. However, when KCI in the presence of a high concentration of histidine (25 mM) was infused through the microdialysis probe, KCI 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.

Keywords: Depolarization, Potassium chloride, Histidine, Hydroxyl radical, Microdialysis

Copyrightゥ The Japanese Pharmacological Society 1999

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