Antiulcer drugs and gastric mucosal integrity. Effects of misoprostol, 16,16-dimethyl PGE2, and cimetidine on hemodynamics and metabolic rate in canine gastric mucosa.
Although prostaglandins (PGs) of the E series have gastric antisecretory and cytoprotective properties, many have different effects on the barrier integrity of the gastric mucosa. The direct effect of antiulcer drugs on gastric mucosal blood flow, mucosal barrier permeability, and metabolic rate have not been adequately studied. These factors are important in the defense of the gastric mucosa. Part of the difficulty relates to the possible influence of gastric mucosal blood flow on gastric acid secretion. To rule out this confounding factor, omeprazole can be used to reveal the true pharmacologic effects of these antiulcer drugs independent of the effect of gastric secretion per se. The study examined the effects of 16,16-dimethyl PGE2 (dmPGE2), misoprostol, and cimetidine on gastric mucosal blood flow, oxygen consumption, potential difference (PD), electrolytes, and fluid flux using the ex vivo gastric chamber dog model. The PGs were administered intraluminally with an isotonic acid solution; cimetidine was administered by arterial infusion. None of the drug treatments had any significant effect on mean systemic arterial pressure, arterial blood gases, body temperature, or oxygen consumption. dmPGE2 significantly (P less than 0.001) decreased PD and enhanced the electrolytes (Na+, K+) and fluid flux across the mucosa (P less than 0.05). Misoprostol significantly increased gastric mucosal blood flow (P less than 0.02) and fluid efflux but decreased PD values. Cimetidine did not have any significant effects on barrier or metabolic functions of the stomach. These results suggest that a considerable difference exists in the pharmacology of gastric antisecretory drugs in relation to their effect on several factors affecting gastric mucosal integrity.
Larsen
K R
KR
Department of Medicine, School of Medicine, University of Utah Salt Lake City, Utah.
Dajani
E Z
EZ
Ives
M M
MM
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D016595:Misoprostol / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects
D000897:Anti-Ulcer Agents; D015221:Potassium Channels; D015222:Sodium Channels; D016595:Misoprostol; D002927:Cimetidine; D009853:Omeprazole; D015064:16,16-Dimethylprostaglandin E2