Effects of a prostacyclin analog, U-68,215, on gastric acid secretion, gastric emptying and systemic blood pressure in primates.
The effect of the prostacyclin analog U-68,215 on gastric function and systemic blood pressure was evaluated in a primate model. Starting 30 min after histalog (1 mg/kg s.c.), gastric acid secretion and gastric emptying were determined over a 30-min period using a 99mTc-diethylene triamine pentaacetic acid dilution technique. Each animal then received an intragastric bolus of 0, 25, 50 or 100 micrograms/kg of U-68,215 and, after a 30-min equilibration period, gastric function was determined for an additional 60 min (histalog + U-68,215). Systemic blood pressure and heart rate were measured periodically using a pressure cuff and a Korotkoff microphone. U-68,215 produced a 94% maximum suppression of acid output from 60 to 90 min after 100 micrograms/kg U-68,215. Gastric emptying was significantly inhibited by all doses of U-68,215, and no diarrhea was observed in response to any dose of U-68,215. Systolic blood pressure was significantly inhibited (P less than .05) only after the 100 micrograms/kg, whereas diastolic blood pressure was reduced significantly (P less than .05) by both 50 and 100 micrograms/kg and was positively correlated with acid secretion (r = .53; P less than .05). These data demonstrate that U-68,215 produces a significant inhibition of acid secretion without the stimulatory effect on gastric emptying induced by PGE analogs. Thus, prostacyclin analogs may represent an attractive alternative to PGE analogs in the treatment of peptic ulcer disease.
Shea-Donohue
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Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Kandasamy
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Dubois
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D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male
D000897:Anti-Ulcer Agents; C047477:U 68215; D011464:Epoprostenol