CHANGES IN CARDIAC ELECTROPHYSIOLOGY, MORPHOLOGY, TISSUE BIOCHEMISTRYAND VASCULAR REACTIONS IN GLUTATHIONE DEPLETED ANIMALS

The effects of acute and chronic glutathione depletion (single i.p. in jection of 3 mmol/kg L-buthionine-S,R-sulphoximine and 2 mmol/kg for 4 days) on heart action potential (AP) characteristics, electronmicrosc opy, cytochemistry and biochemistry and vascular contractility and nit ric oxide-mediated relaxation were studied in rats and guinea pigs. In guinea pig cardiac preparations both acute and chronic glutathione de pletion caused a significant decrease of maximum rate of rise of depol arization phase and duration of action potential AP(APD) at 25, 50, an d 90% of repolarization but did not modify the other AP parameters. Th e contractile responses of helically cut aortic strips to norepinephri ne were not altered by chronic glutathione depletion but the relaxing responses of precontracted preparations to acetylcholine were signific antly reduced both in rats and guinea pigs. Morphologically there were indications of permeability changes, intracellular and interstitial e dema and myofilament damage in the myocardium. There was also a decrea se in cytochromoxydase and succinyl dehydrogenase activities both in r ats and guinea pigs. The present data suggest that glutathione depleti on may influence the Na+ and K+ channel activities, causes morphologic al and biochemical changes in cardiac preparations and may interfere w ith nitric oxide generation or its action in aortic strips.