ANTIOXIDANT-SENSITIVE SHORTENING OF VENTRICULAR ACTION-POTENTIAL IN HYPERTHYROID RATS IS INDEPENDENT OF LIPID-PEROXIDATION

The effects of substances able to reduce peroxidative processes on thy roid hormone-induced electrophysiological changes in ventricular muscl e fibres were examined. For this study, 60 day old euthyroid and hyper thyroid rats were used. One group of hyperthyroid rats was untreated a nd the others were treated with vitamin E, N-acetylcysteine, and chole sterol, respectively. Hyperthyroidism was elicited by 10 day treatment with daily i.p. injections of triiodothyronine (10 mu g/100 g body we ight). Vitamin E and N-acetylcysteine were administered for IO days by daily i.m. injections (20 mg/100 g body weight) and daily i.p. inject ions (100 mg/100 g body weight), respectively. Cholesterol was adminis tered by cholesterol-supplemented diet (4%) from day 30. Hyperthyroidi sm induced a decrease in the whole antioxidant capacity and an increas e in both lipid peroxidation and susceptibility to oxidative stress. V itamin E and N-acetylcysteine administration to hyperthyroid rats led to reduction in lipid peroxidation and susceptibility to oxidative str ess and to increase in antioxidant level, while the diet addition of c holesterol decreased lipid peroxidation but did not modify the other p arameters. The hyperthyroid state was also associated with a decrease in the duration of the ventricular action potential recorded in vitro. The vitamin E and N-acetylcysteine administration attenuated the thyr oid hormone-induced changes in action potential duration, which was ho wever, significantly different from that of the euthyroid rats. In con trast, cholesterol supplementation did not modify the electrical activ ity of hyperthyroid heart. These results demonstrate that the triiodot hyronine effects on ventricular electrophysiological properties are me diated, at least in part, through a membrane modification involving a free radical mechanism. Moreover, they indicate that the antioxidant-s ensitive shortening of action potential duration induced by thyroid ho rmone is likely independent of enhanced peroxidative processes in sarc olemmal membrane. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.