Background/aims: 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.