Changes in cardiac electrophysiology, morphology, tissue biochemistry and vascular reactions in glutathione depleted animals.
The effects of acute and chronic glutathione depletion (single i.p. injection of 3 mmol/kg L-buthionine-S,R-sulphoximine and 2 mmol/kg for 4 days) on heart action potential (AP) characteristics, electronmicroscopy, cytochemistry and biochemistry and vascular contractility and nitric oxide-mediated relaxation were studied in rats and guinea pigs. In guinea pig cardiac preparations both acute and chronic glutathione depletion caused a significant decrease of maximum rate of rise of depolarization phase and duration of action potential AP(APD) at 25, 50, and 90% of repolarization but did not modify the other AP parameters. The contractile responses of helically cut aortic strips to norepinephrine were not altered by chronic glutathione depletion but the relaxing responses of precontracted preparations to acetylcholine were significantly reduced both in rats and guinea pigs. Morphologically there were indications of permeability changes, intracellular and interstitial edema and myofilament damage in the myocardium. There was also a decrease in cytochromoxydase and succinyl dehydrogenase activities both in rats and guinea pigs. The present data suggest that glutathione depletion may influence the Na+ and K+ channel activities, causes morphological and biochemical changes in cardiac preparations and may interfere with nitric oxide generation or its action in aortic strips.
Pacher
P
P
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
Kecskemeti
V
V
Ronai
A Z
AZ
Balogh
I
I
Szalai
G
G
Matkovics
B
B
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002319:Cardiovascular System / Q000378:metabolism* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000096:biosynthesis / Q000172:deficiency* / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; D005978:Glutathione