The role of nitric oxide in the inhibition of gastric epithelial proliferation in portal hypertensive rats.
OBJECTIVE
Portal hypertension is associated with inhibition of gastric epithelial proliferation and increased gastric nitric oxide synthase activity. Whether the nitric oxide inhibits gastric epithelial proliferation is unclear.


METHODS
Portal vein ligation was performed to induce portal hypertension in rats. The rats were treated for 7 days with either vehicle or N(G)-nitro-L-arginine methyl ester (L-NAME) at 5 mg/kg or 25 mg/kg doses (gastric gavage, twice a day). Sham-operated rats treated with vehicle served as controls. Hemodynamic parameters were measured using radiolabeled microspheres in anesthetized animals. Gastric epithelial proliferation was assessed by evaluating the proliferative cell nuclear antigen labeling index.


RESULTS
The cardiac index and gastric fundic blood flow were higher, and the gastric fundic proliferative cell nuclear antigen labeling index was lower in the portal hypertensive rats than in the controls. In portal hypertensive rats, the 5 mg/kg dose of L-NAME decreased the cardiac index and increased the gastric fundic proliferative cell nuclear antigen labeling index to levels similar to those found in the controls, but did not affect gastric fundic blood flow significantly. The 25 mg/kg dose of L-NAME further decreased both the cardiac index and the gastric fundic blood flow, but did not affect the gastric proliferative cell nuclear antigen labeling index significantly.


CONCLUSIONS
In portal hypertensive rats, the correction of systemic hyperdynamic circulation by NO inhibition is associated with normalization of gastric epithelial proliferation. Excessive nitric oxide may inhibit gastric epithelial proliferation in portal hypertension.
Baatar
D
D
First Department of Surgery, Oita Medical University, Japan. baatar@oita-med.ac.jp
Kitano
S
S
Yoshida
T
T
Bandoh
T
T
Ninomiya
K
K
Tsuboi
S
S
D000818:Animals; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000473:pathology; D006439:Hemodynamics / Q000502:physiology; D006975:Hypertension, Portal / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000201:enzymology / Q000473:pathology*
D004791:Enzyme Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester