NO-mediated vasodilation in the rat liver. Role of hepatocytes and liver endothelial cells.
OBJECTIVE
Nitric oxide (NO) is a potent vasodilator. We investigated the mechanisms responsible for this effect in the liver.


METHODS
Isolated perfused rat liver and cultures of endothelial sinusoidal cells and hepatocytes were used.


RESULTS
L-arginine (10(-3) M) and NO donor Sin-1 (10(-5) M) respectively increased the liver flow by 52% (p<0.01) and 93% (p<0.01) vs controls. The NO synthase inhibitor Nw-nitro-L-arginine (10(-3) M) and the guanylate cyclase inhibitor methylene blue (10(-5) M) respectively decreased the basal liver flow by 26% and 16% (p<0.05) and inhibited the vasodilating effects of L-arginine. L-arginine (10(-3) M) increased nitrite concentration in hepatocyte culture (77.25+/-7.40 micromol x l(-1) vs 14.70+/-3.55 micromol x l(-1) in controls; p<0.01) and in liver endothelial cell culture (0.36+/-0.09 micromol x l(-1) vs 0.12+/-0.05 micromol x l(-1) in controls; p<0.05). Nw-nitro-L-arginine inhibited the basal production and abolished the L-arginine-induced production of nitrites both in hepatocyte and in liver endothelial cell cultures. The concentration of nitrites in the hepatocyte supernatant rose from 14.70+/-3.55 micromol x l(-1) to 150.50+/-45.55 micromol x l(-1) in the presence of a combination of interleukin-1beta, TNF alpha and interferon gamma.


CONCLUSIONS
Under basal conditions, NO regulates the vascular tone of liver circulation. Both liver endothelial cells and hepatocytes can be implicated. NO production by hepatocytes may increase during inflammation.
Zhang
B
B
Laboratoire de Recherche Chirurgicale, Faculté de Médecine Cochin-Port-Royal, Hôpital Cochin, Paris, France.
Borderie
D
D
Sogni
P
P
Soubrane
O
O
Houssin
D
D
Calmus
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D008751:Methylene Blue