Hitoshi Moritomo

Study of 16,16-Dimethyl Prostaglandin E2 for Prevention of Stress Ulcer after Hepatectomy of Experimental Cirrhotic Liver and Its Influence on Hepatic Regeneration

The influence of 16,16-dimethyl prostaglandin E2 (16,16-dm PGE2; an agent used for the prevention of stress ulcer after hepatectomy of the cirrhotic liver) on liver regeneration after hepatectomy was studied in rats. The following results were obtained. Ulceration after the stress of 6 h of water immersion was markedly suppressed in rats treated with 30 r/kg of 16,16-dmPGE2 as compared with the untreated controls. In animals that received hepatectomy alone, the gastric pH and gastric mucosal blood flow showed significant reduction from the preoperative levels. In animals that received hepatectomy plus 16,16-dmPGE2 treatment the postoperative reduction in the gastric pH and gastric mucosal blood flow was suppressed, suggesting the effectiveness of 16,16-dmPGE2 treatment in the prevention of stress ulcer after hepatectomy of the cirrhotic liver. The 3H-thymidine uptake percentage and thymidine activity 24 h after hepatectomy and the DNA content 30 h after hepatectomy were significantly higher in animals treated with 16,16-dmPGE2 than in the untreated controls. In animals that were treated intraperitoneally with 50 mg/kg of indomethacin 6 h before hepatectomy the mitotic index 30 h after hepatectomy was markedly lower than that in untreated controls. This indomethacin-induced reduction in the mitotic index tended to be normalized by treatment with 16,16-dmPGE2. These results suggest that 16,16-dmPGE2 treatment effectively prevents stress ulcer and favorably affects hepatic regeneration after hepatectomy of the cirrhotic liver.

Inhibitory Effect of Peptide YY on Gastric Acid Output in Rats

The administration of peptide YY (PYY: 0.8, 1.6 and 3.2 nmol/kg/h, i.v.) to fasting rats inhibited not only baclofen (2 mg/kg, s.c.)-stimulated gastric acid output and gastric mucosal blood flow, but also pentagastrin (8 micrograms/kg/h, i.v.)-stimulated gastric acid output. PYY (3.2 nmol/kg/h) reduced baclofen-induced acid output more than pentagastrin-induced acid output, i.e., by 61.8 +/- 11.5% compared to 35.3 +/- 8.2%. PYY inhibited acetylcholine (ACh) release from cholinergic nerve endings of gastric body evoked by electrical transmural stimulation (ETS: 1 msec, 10 V, 3 Hz, 30 sec) by 47.2 +/- 3.5%. The mechanism of the inhibitory effect of PYY on gastric acid output seems to involve decreased gastric mucosal blood flow and reduced ACh release from cholinergic nerves.

The mechanism of acute gastric ulcer after induced hemorrhagic shock.

Changes in gastric mucosal blood flow were investigated for their relationship to gastric mucosal prostaglandin E2 (PGE2) and noradrenaline (NA) in rats with hemorrhagic shock. The results were as follows: 1) Gastric mucosal blood flow and NA decreased after hemorrhage. Gastric mucosal PGE2 initially increased after exsanguination and then markedly decreased. 2) Administration of NA before hemorrhage resulted in an increase of PGE2. However, the PGE2 value for animals receiving NA after hemorrhage was not different from that of non-NA-treated group. 3) Pre-treatment with PGE2 suppressed the reduction in both gastric mucosal blood flow and NA and the development of ulcer. These results suggest that the increase in gastric mucosal PGE2 in the early stage of shock might represent a phenomenon of adaptation by the adrenergic activation, and the decrease in PGE2 in the late stage might result from impaired synthesis of PGE2 due to persistent hypoxia and might be one of the possible factors in ulcer formation.

Impaired response of gastric vessels to prostaglandin E2 in rats with persistent obstructive jaundice

We investigated the response of gastric vessels to prostaglandin (PG) E2 after intra-duodenal release of bile in rats with obstructive jaundice. The animals were divided into four groups according to duration of bile duct obstruction (BDO): control and 1 week (W), 2W, and 3W groups. Prolonged BDO decreased gastric mucosal blood flow (BF) significantly. The BF recovered after the release of BDO in the 1W and 2W groups, but not in the 3W group. BDO decreased PGE2 content in gastric mucosa in the 1W, 2W, and 3W groups. PGE2 decreased vascular perfusion pressure of the isolated stomach in the control and 2W groups, but not in the 3W group. The response of gastric vessels to PGE2 was poor in the 3W group compared with the control and 2W groups. Decreased PGE2 in the gastric mucosa and decreased response of gastric vessels to PGE2 may affect gastric blood flow in obstructive jaundice.