Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver.
This study was designed to investigate the mechanism for ethanol-induced hepatic vasoconstriction in isolated perfused rat liver. Upon initiation of ethanol infusion into the portal vein at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phenomenon). Endothelin-1 antiserum significantly inhibited this ethanol-induced hepatic vasoconstriction by 45-80%. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, after the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phenomenon and sustained the vasoconstriction. This study supports the hypothesis that two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide, regulate hepatic vascular tone in the presence of ethanol.
Oshita
M
M
First Department of Medicine, Osaka University Medical School, Japan.
Takei
Y
Y
Kawano
S
S
Yoshihara
H
H
Hijioka
T
T
Fukui
H
H
Goto
M
M
Masuda
E
E
Nishimura
Y
Y
Fusamoto
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000276:immunology / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D007106:Immune Sera / Q000494:pharmacology; D008099:Liver / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D016232:Endothelins; D007106:Immune Sera; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000431:Ethanol; D001120:Arginine