Intraportal nicotine infusion in rats decreases hepatic blood flow through endothelin-1 and both endothelin A and endothelin B receptors.
Smoking has been demonstrated to aggravate liver injury. Nicotine, a major pharmacological component of tobacco smoke, affects a multitude of functions. Smoking and nicotine induce synthesis of endothelin (ET)-1. The effect of intraportal infusion of nicotine on hepatic circulation and an involvement of ET-1 and ET receptor in the action of nicotine were investigated in rats. Nicotine (0-100 microg/kg/h) was infused into the portal vein of urethane-anesthetized rats, and changes of hepatic blood flow were evaluated. Intraportal infusion of nicotine dose-dependently decreased hepatic blood flow and increased portal pressure without any alteration of heart rate or arterial blood pressure. This action of intraportal nicotine was completely abolished by pretreatment of ET-1 antibody. Either BQ485 (ET(A) receptor antagonist) or BQ788 (ET(B) receptor antagonist) partially reversed the effect of nicotine, and combination of BQ788 and BQ485 completely abolished it. These findings suggest that nicotine inhibits hepatic circulation through ET-1, and ET(A) and ET(B) receptor.
Hashimoto
Takashi
T
Department of Gastroenterology, Dokkyo University School of Medicne, Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan.
Yoneda
Masashi
M
Shimada
Tadahito
T
Kurosawa
Mieko
M
Terano
Akira
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001381:Azepines; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D018722:Nicotinic Agonists; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C083116:BQ 485; C086539:BQ 788; D009538:Nicotine