Role of oxidative stress in catecholamine-induced changes in cardiac sarcolemmal Ca2+ transport

Although an excessive amount of circulating catecholamines is known to indu ce cardiomyopathy, the mechanisms are poorly understood. This study was und ertaken to investigate the role of oxidative stress in catecholamine-induce d heart dysfunction, Treatment of rats for 24 h with a high dose (40 mg/kg) of a synthetic catecholamine, isoproterenol, resulted in increased left ve ntricular end diastolic pressure, depressed rates of pressure development, and pressure decay as well as increased myocardial Ca2+ content. The increa sed malondialdehyde content, as well as increased formation of conjugated d ienes and low glutathione redox ratio were also observed in hearts from ani mals injected with isoproterenol, Furthermore, depressed cardiac sarcolemma l (SL) ATP-dependent Ca2+ uptake, Ca2+-stimulated ATPase activity, and Na+- dependent Ca2+ accumulation were detected in experimental hearts. All these catecholamine-induced changes in the heart were attenuated by pretreatment of animals with vitamin E, a well-known antioxidant (25 mg/kg/day for 2 da ys). Depressed cardiac performance, increased myocardial Ca2+ content, and decreased SL ATP-dependent, and Na+-dependent Ca2+ uptake activities were a lso seen in the isolated rat hearts perfused with adrenochrome, a catechola mine oxidation product (10 to 25 mug/ml). Incubation of SL membrane with di fferent concentrations of adrenochrome also decreased the ATP-dependent and Na+-dependent Ca2+ uptake activities. These findings suggest the occurrenc e of oxidative stress, which may depress the SL Ca2+ transport and result i n the development intracellular Ca2+ overload and heart dysfunction in cate cholamine-induced cardiomyopathy. (C) 2001 Academic Press.