Role of gastric oxidative stress and nitric oxide in formation of hemorrhagic erosion in rats with ischemic brain.
OBJECTIVE
To investigate the role of gastric oxidative stress and nitric oxide (NO) in the formation of gastric hemorrhagic erosion and their protection by drugs in rats with ischemic brain.


METHODS
Male Wistar rats were deprived of food for 24 h. Under chloral hydrate (300 mg/kg) anesthesia, bilateral carotid artery ligation was performed. The pylorus and carotid esophagus of the rats were also ligated. The stomachs were then irrigated for 3 h with either normal saline or simulated gastric juice containing 100 mmol/L HCl plus 17.4 mmol/L pepsin and 54 mmol/L NaCl. Rats were killed and stomachs were dissected. Gastric mucosa and gastric contents were harvested. The rat brain was dissected for the examination of ischemia by triphenyltetrazolium chloride staining method. Changes in gastric ulcerogenic parameters, such as decreased mucosal glutathione level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples, were measured.


RESULTS
Bilateral carotid artery ligation produced severe brain ischemia (BI) in rats. An exacerbation of various ulcerogenic parameters and mucosal hemorrhagic erosions were observed in these rats. The exacerbated ulcerogenic parameters were significantly (P<0.05) attenuated by antioxidants, such as exogenous glutathione and allopurinol. These gastric parameters were also improved by intraperitoneal aminoguanidine (100mg/kg) but were aggravated by N(G)-nitro-L-arginine-methyl ester (L-NAME: 25 mg/kg). Intraperitoneal L-arginine (0-500 mg/kg) dose-dependently attenuated BI-induced aggravation of ulcerogenic parameters and hemorrhagic erosions that were reversed by L-NAME.


CONCLUSIONS
BI could produce hemorrhagic erosions through gastric oxidative stress and activation of arginine-nitric oxide pathway.
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 70101, China. crhung@mail.ncku.edu.tw
Chen-Road
CR
Hung
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000209:etiology* / Q000473:pathology; D005978:Glutathione / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D000493:Allopurinol; D001120:Arginine; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester