L-Arginine protects and exacerbates ethanol-induced rat gastric mucosal injury.
OBJECTIVE
We have previously demonstrated that 60% ethanol (EtOH) increases macromolecular leakage and induces focal lesion formation in areas of permanent flow stasis within gastric mucosal vessels. Nitric oxide (NO) may prevent lesion formation by inhibiting leakage. This study used fluorescent in vivo microscopy to investigate (i) whether L-arginine (NO precursor) prevented EtOH induced injury and (ii) the mechanisms of protection.


METHODS
Experiments were carried out on anaesthetized rats (hypnorm/diazepam) receiving either intra-arterial fluorescein isothiocyanate-bovine serum albumin (0.2 mL/100 g), a marker for quantitating leakage, or Acridine red (0.1 mL/100 g) which labels leukocytes. Animals then received 100, 300 or 500 mg/kg L-arginine (i.a.) followed by 60% EtOH or distilled water, topically applied to the gastric mucosa (n = 6 for each group). Vessel diameter, macromolecular leakage of labelled albumin from post capillary venules (PCV) and capillaries and leukocyte activity were quantitated using image analysis.


RESULTS
L-Arginine (100 mg/kg) did not increase vessel diameter or prevent EtOH-induced lesion formation and leakage. Both 300 mg/kg and 500 mg/kg alone induced significant and sustained increases in PCV diameter after 15 (P< 0.01) and 5 min (P< 0.001), respectively. Lesion formation was only prevented by 300 mg/kg L-arginine, whereas 500 mg/kg exacerbated haemorrhagic lesion formation over the entire exposed mucosa. Neither 300 mg/kg nor 500 mg/kg L-arginine prevented leakage following EtOH. No leukocyte activity was observed following EtOH with or without L-arginine pretreatment.


CONCLUSIONS
L-Arginine (300 mg/kg) prevented lesion formation. The mechanism of protection probably involved the increased blood flow in the dilated PCV and not the inhibition of leakage. The combined effects of EtOH and the possible high NO levels exacerbate gastric mucosal damage despite the increases observed in vessel diameter.
Kalia
N
N
Department of Surgical and Anaesthetic Sciences, Royal Hallamshire Hospital, Sheffield, United Kingdom. N.Kalia@sheffield.ac.uk
Bardhan
K D
KD
Reed
M W
MW
Jacob
S
S
Brown
N J
NJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology* / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007261:Infusions, Intra-Arterial; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D018709:Statistics, Nonparametric; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D014664:Vasodilation / Q000187:drug effects
D000431:Ethanol; D001120:Arginine