Protective effect of vanadate on oxyradical-induced changes in isolated perfused heart.
In order to examine the mechanisms of the beneficial effects of vanadate on cardiac dysfunction in chronic diabetes, rat hearts were perfused with xanthine plus xanthine oxidase, an oxyradical generating system in the absence or presence of vanadate. The heart failed to generate contractile force and increased the resting tension markedly within 5 min of perfusion with xanthine plus xanthine oxidase. These changes were prevented by the addition of 4 microM vanadate in the perfusion medium. The protective effects of vanadate on the loss of developed tension and increased resting tension due to xanthine plus xanthine oxidase were dose-dependent (0.1-5 microM). Perfusion of the hearts with glucose-free medium did not abolish the protective actions of vanadate. The sarcolemmal Ca(2+)-pump (ATP-dependent Ca2+ uptake and Ca(2+)-stimulated ATPase) and Na(+)-dependent Ca2+ uptake activities were decreased upon perfusing the hearts with a medium containing xanthine plus xanthine oxidase for 5 min; these effects were prevented by the addition of 2-4 microM vanadate in the perfusion medium. The signals for superoxide radicals produced by xanthine plus xanthine oxidase, as detected by electron paramagnetic resonance spectroscopic technique, were inhibited by 5-100 microM vanadate. These results suggest that vanadate is an oxyradical scavenger and thus may prevent heart dysfunction under some pathological conditions by its antioxidant action.
Matsubara
T
T
Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Musat-Marcu
S
S
Misra
H P
HP
Dhalla
N S
NS
D000818:Animals; D002118:Calcium / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005609:Free Radicals / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014638:Vanadates / Q000494:pharmacology*; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology*
D005609:Free Radicals; D014970:Xanthines; D019820:Xanthine; D014638:Vanadates; D014969:Xanthine Oxidase; D002118:Calcium