title: Possible mechanism responsible for mechanical dysfunction of ischemic myocardium: a role of oxygen free radicals.
abstract: It has been proposed that a major target organelles damaged by the ischemic process, probably by the oxygen free radicals generated, is the portion of the excitation-contraction coupling system that regulates Ca2+ delivery (the sarcoplasmic reticulum and sarcolemma) to the contractile proteins. We tested this hypothesis by studying the effect of in vitro generation of oxygen free radicals from xanthine-xanthine oxidase system or dihydroxyfumarate (DHF)/Fe3+-ADP system on Ca2+ flux behavior of canine cardiac sarcoplasmic reticulum (SR); sarcolemmal (Na+, K+)-ATPase and Na+-Ca2+ exchange activities; and myofibrillar (Ca2+, Mg2+)-ATPase activity. Generation of oxygen free radicals by xanthine oxidase acting on xanthine as a substrate increased the passive Ca2+ efflux and decreased intravesicular Ca2+ with no effect on active Ca2+ influx (Ca2+-ATPase) of SR vesicles. Similar exposure of sarcolemmal vesicles to xanthine plus xanthine oxidase stimulated Na+-Ca2+ exchange activity. When sarcolemmal vesicles were incubated with DHF plus Fe3+-ADP, (Na+, K+)-ATPase activity was decreased. It is postulated that the SR Ca2+ efflux pathways but not catalytic activity of the Ca2+ pump and sarcolemmal (Na+, K+)-ATPase involving Na+-Ca2+ exchange activity are altered by oxygen free radicals, and such changes may partly account for the occurrence of intracellular Ca2+ overload during the course of myocardial ischemia. Interestingly, oxygen free radicals from xanthine-xanthine oxidase system had no effect on myofibrillar pCa-ATPase curve. From this set of observations we would hypothesize that the SR and sarcolemma may be the principal target organelles of oxygen free radicals attack in the ischemic injury and not the contractile proteins per se.
authors.affiliation: Department of Pharmacology, Kanagawa Dental College, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Okabe
authors.forename: R
authors.initials: R
authors.lastname: Fujimaki
authors.forename: M
authors.initials: M
authors.lastname: Murayama
authors.forename: H
authors.initials: H
authors.lastname: Ito
mesh_terms: D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003327:Coronary Disease / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D005609:Free Radicals; D006321:Heart / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009210:Myofibrils / Q000201:enzymology; D010100:Oxygen / Q000378:metabolism / Q000502:physiology*; D012508:Sarcolemma / Q000201:enzymology / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D005609:Free Radicals; D012964:Sodium; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen; D002118:Calcium