Role of endogenous nitric oxide in ischemia-reperfusion injury in rat liver.
Evidence has accumulated that oxygen-derived free radicals contribute to the cellular damage induced by ischemia-reperfusion. It has been suggested that nitric oxide (NO) may act as a protective factor in ischemia-reperfusion injury since NO increases blood flow and may scavenge oxyradicals. Nevertheless, controversy exists as to the role of NO. This study was designed to clarify the role of endogenous NO in ischemia-reperfusion-induced liver injury in rats in vivo. Wistar rats weighing 250-300 g were divided into three groups: (1) untreated group (Control); (2) NG-nitro-L-arginine, a specific inhibitor of NO production (L-NNA); and (3) L-arginine-pretreated L-NNA group (AR+L-NNA). Occlusion of all vessels to the median and left hepatic lobes (60 min) was followed by reperfusion for 1 or 24 hr. L-NNA was administered before ischemia as a 10 mg/kg bolus. L-Arginine was given just before L-NNA administration as a 100 mg/kg bolus. Administration of L-NNA resulted in endothelial cell injury characterized by the elevation of serum hyaluronic acid as well as the reduction of hepatic tissue blood flow, and the recovery of hepatic adenosine triphosphate was depressed compared with the control after both 1 and 24 hr of reperfusion. Furthermore, the leakages of various liver enzymes and lipid peroxide were also increased, associated with histological damage. This effect of L-NNA was completely abolished by pretreatment with L-arginine. These results suggest that endogenous NO provides a protective effect against ischemia-reperfusion injury in rat liver.
Department of Surgery II, Nagoya University School of Medicine, Japan.
H
H
Kobayashi
T
T
Nonami
T
T
Kurokawa
Y
Y
Takeuchi
A
A
Harada
A
A
Nakao
H
H
Takagi
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*
D000227:Adenine Nucleotides; D008054:Lipid Peroxides; D019335:Nitroarginine; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase