Increase in hepatic tissue blood flow by teprenone.
The major objective of the present study was to evaluate mechanisms by which teprenone, a gastric mucosal protecting agent, increases hepatic mucosal blood flow using male Sprague-Dawley rats. Hepatic and gastric blood flow was measured using a laser blood flow meter after administration of teprenone, dissolved in Tween 80, into the inferior vena cava. Teprenone itself increased hepatic and gastric blood flow. It also increased hepatic and gastric blood flow in rats with acute hepatic disorders due to carbon tetrachloride (CCL4) and improved histological changes, such as inflammatory cell infiltration and fatty changes in the liver. The fact that blood endothelin (ET) concentrations increased after administration of teprenone suggest that teprenone has great affinity for ET beta receptors and shows ET beta-receptor antagonist-like effects. Hepatic blood flow decreased after administration of N-nitro-L-arginine methyl ester, a nitric oxide (NO) synthetase inhibitor, suggesting that teprenone increase NO activity. Teprenone was thought to increase hepatic and gastric blood flow by different mechanisms, because it increased gastric mucosal prostaglandin E2 concentrations.
Department of Gastroenterology, Aoyama Hospital, Tokyo Women's Medical College, Japan.
T
T
Kurihara
Y
Y
Kitamura
Y
Y
Adachi
M
M
Obuchi
K
K
Abe
M
M
Akimoto
H
H
Hashimoto
H
H
Ishiguro
A
A
Niimi
A
A
Maeda
M
M
Shigemoto
K
K
Yamashita
I
I
Yokoyama
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D019332:Endothelin-1 / Q000097:blood; D005753:Gastric Mucosa / Q000098:blood supply; D008099:Liver / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013268:Stimulation, Chemical
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D019332:Endothelin-1; D009569:Nitric Oxide; C031049:geranylgeranylacetone