Endogenous Nitric Oxide as a Mediator of Gastric Mucosal Vasodilatation During Acid Secretion

Abstract 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, N G -monomethyl-l-arginine (12.5 and 50 mg/kg), which dose-dependently increased systemic arterial blood pressure, did not affect resting acid output. However, N G -monomethyl-l-arginine significantly reduced resting gastric mucosal blood flow at the higher dose, as determined by hydrogen gas clearance. Infusion of pentagastrin (80 μg kg −1 · h −1 ) stimulated gastric acid secretion and elevated gastric mucosal blood flow. Pretreatment with N G -monomethyl-l-arginine (12.5 mg/kg IV) did not affect this stimulation of acid output but substantially attenuated (by 65% ± 10%; P N G -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, N G -monomethyl-l-arginine (50 mg/ kg IV) did not affect the acid secretory response but induced a 76% ± 8% inhibition ( P N G -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.