L-arginine and endogenous nitric oxide protect the gastric mucosa from endothelin-1-induced gastric ulcers in rats.
We have reported that endothelin-1 induces gastric ulcer characterized by a potent long-lasting vasoconstriction of the regional microvasculature. Nitric oxide synthesized from L-arginine has been shown to regulated gastric mucosal blood flow, and inhibition of its synthesis has been shown to delay the healing of gastric ulcers. We examined the effect of exogenous L-arginine and the inhibition of nitric oxide synthesis on the development of endothelin-1-induced gastric ulcers. In rats anesthetized with urethane, a continuous intravenous infusion of L- or D-arginine (10 mg.kg-1.min-1) was followed, 15 min later, by a submucosal injection of endothelin-1 (200 pmol/kg) in the anterior wall of the gastric body. In another group, rats were intravenously pretreated with N omega-nitro-L-arginine-methyl ester (1-10 mg/kg), a nitric oxide synthesis inhibitor, and then injected with endothelin-1 (40 pmol/kg). Twenty-four h later, L-arginine, but not D-arginine, had significantly reduced the extent and the severity of the endothelin-1-induced ulcer (mucosal wall damage, 18.11 +/- 4.79% and 88.14 +/- 7.06%, respectively; mean +/- SD, P < 0.001), and the nitric oxide synthesis inhibitor (10 mg/kg) had increased the endothelin-1-induced mucosal damage (ulcer length, 3.8 +/- 1.2 mm and 1.1 +/- 0.2 mm, respectively, P < 0.01). Continuous gastric mucosal blood flow measurements showed that L-arginine antagonized the endothelin-1-induced vasoconstriction. L-arginine protected the gastric mucosa from the ulcerogenic action of endothelin-1 and antagonized its vasoconstrictive action. The inhibition of endogenous nitric oxide potentiated the ulcerogenic effect of endothelin-1 on rat gastric mucosa.
Lazaratos
S
S
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
Kashimura
H
H
Nakahara
A
A
Fukutomi
H
H
Osuga
T
T
Goto
K
K
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001783:Blood Flow Velocity; D016232:Endothelins; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007262:Infusions, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D016232:Endothelins; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester