NO-mediated vasodilation in the rat liver : Role of hepatocytes and liver endothelial cells

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 μmol • 1−1 vs 14.70±3.55 μmol • 1−1 in controls; p<0.01) and in liver endothelial cell culture (0.36±0.09 μmol • 1−1 vs 0.12±0.05 μmol • 1−1 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 μmol−1 • 1− to 150.50±45.55 μmol • 1−1 in the presence of a combination of interleukin-1β, TNF a and interferon γ. 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.