Renal failure increases gastric mucosal blood flow and acid secretion in rats: role of endothelium-derived nitric oxide.
Because of the contradictory findings in clinical studies, and the complete lack of animal studies, the purpose of this investigation was to characterize the changes in gastric mucosal blood flow (GMBF) and acid secretion in an animal model of chronic renal failure. Rats with chronic renal failure induced by partial kidney infarction had a significantly higher basal GMBF and lower gastric vascular resistance than control rats. The gastric acid secretory and mucosal hyperemic response to pentagastrin were markedly enhanced in renal failure rats. Because endothelial-derived nitric oxide (NO) is an endogenous vasodilator that regulates gastric vascular tone, we hypothesized that NO mediates the gastric hyperemia of renal failure rats. The administration of N omega-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO formation, produced a significantly greater decrease in GMBF in renal failure rats than in control rats, including a low dose inhibiting the basal hyperemia in renal failure rats but having no effect in control rats. It also attenuated pentagastrin-stimulated GMBF in both groups. In contrast, L-NAME produced a similar decrease in basal skeletal muscle blood flow in both renal failure and control rats. We conclude that in the renal failure rat 1) there is an increased basal GMBF and pentagastrin-stimulated acid output and GMBF, and 2) this gastric mucosal hyperemia is mediated by NO.
Quintero
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Medical Service, Veterans Affairs Medical Center, West Los Angeles, California.
Guth
P H
PH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply*; D006439:Hemodynamics; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D009132:Muscles / Q000098:blood supply; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D010418:Pentagastrin; D019331:NG-Nitroarginine Methyl Ester