The influence of the nitric oxide synthase inhibitor L-NOARG on the effects of ethanol in rats after acute ethanol administration.
The aim of this work was to study the effects of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (L-NOARG) on the sedative and toxic effects of ethanol in rats. Ethanol at a dose of 3 g/kg, intraperitoneally induced sleep in rats (sleep time: 111.2+/-10.3 min.). Administration of the nitric oxide synthase inhibitor L-NOARG (20 and 40 mg/kg, intraperitoneally) 30 min. before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG at doses of 20 and 40 mg/kg reduced the exploratory activity of rats in the open-field test and significantly enhanced the sedative effect of ethanol in this test. It is possible that this effect is not caused by the interaction of ethanol with nitric oxide pathways but by synergistic CNS depression caused by ethanol and L-NOARG. L-NOARG (20 and 40 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (2 and 3 g/kg). Moreover, the combined administration of ethanol (2 g/kg) and L-NOARG (20 and 40 mg/kg) caused a decrease in the body weight of animals, observed for 14 days. Also, livers of these rats were studied for necrosis and connective tissue reaction. In histological studies L-NOARG at a dose of 40 mg/kg had no effect on hepatic necrosis caused by the acute administration of ethanol but strengthened connective tissue reaction. L-NOARG is widely used in pharmacological studies, including those concerning the effects of ethanol. However, on the basis of our data the possibility of toxic interactions with ethanol should be considered.
Vassiljev
V
V
Department of Pathologic Anatomy and Forensic Medicine, Faculty of Medicine, Tartu University, Estonia.
Mesila
I
I
Väli
M
M
Pokk
P
P
D000818:Animals; D001143:Arousal / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D000431:Ethanol; D019001:Nitric Oxide Synthase