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