Endogenous nitric oxide as a mediator of gastric mucosal vasodilatation during acid secretion.
The role of the endothelium-derived vasodilator, nitric oxide, as a mediator of the increase in gastric mucosal blood flow and as a modulator of the acid secretory response induced by pentagastrin was investigated in the anesthetised rat. Intravenous administration of the selective inhibitor of endogenous nitric oxide synthesis, NG-monomethyl-L-arginine (12.5 and 50 mg/kg), which dose-dependently increased systemic arterial blood pressure, did not affect resting acid output. However, NG-monomethyl-L-arginine significantly reduced resting gastric mucosal blood flow at the higher dose, as determined by hydrogen gas clearance. Infusion of pentagastrin (80 micrograms kg-1.h-1) stimulated gastric acid secretion and elevated gastric mucosal blood flow. Pretreatment with NG-monomethyl-L-arginine (12.5 mg/kg IV) did not affect this stimulation of acid output but substantially attenuated (by 65% +/- 10%; P less than 0.01) the associated increase in gastric mucosal blood flow. Pretreatment with NG-monomethyl-L-arginine (50 mg/kg IV) induced a minor inhibition of pentagastrin-stimulated acid secretion but abolished the increase in gastric mucosal blood flow. When administered during pentagastrin infusion, NG-monomethyl-L-arginine (50 mg/kg IV) did not affect the acid secretory response but induced a 76% +/- 8% inhibition (P less than 0.05) of the elevated gastric mucosal blood flow. The effects of NG-monomethyl-L-arginine on blood pressure, acid secretion, and gastric mucosal blood flow were abolished by pretreatment with the precursor for nitric oxide synthesis, L-arginine (300 mg/kg IV). These findings in the rat suggest that endogenous nitric oxide, synthesized from L-arginine, does not directly modulate the acid secretory response induced by pentagastrin but makes a substantial contribution to the mucosal vasodilatation associated with the stimulation of gastric acid secretion.
Pique
J M
JM
Gastrointestinal Unit, Hospital Clinic, Barcelona, Spain.
Esplugues
J V
JV
Whittle
B J
BJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D010418:Pentagastrin