EFFECTS OF THE NITRIC-OXIDE SYNTHASE INHIBITORS N-G-NITRO-L-ARGININE METHYL-ESTER AND AMINOETHYL-ISOTHIOUREA ON THE LIVER MICROCIRCULATION IN RAT ENDOTOXEMIA

Background/Methods: The question whether nitric oxide protects or impa irs organ perfusion during early endotoxemia has not been completely a nswered, To evaluate the regulative function of nitric oxide on organ microvascular perfusion and leukocyte accumulation during endotoxemia, we studied the influence of a non-selective nitric oxide inhibitor an d a preferential inducible nitric oxide synthase inhibitor (respective ly, N-G-nitro-L-arginine methyl ester and aminoethyl-isothiourea) on l iver microcirculation (intravital fluorescence microscopy) in a rat mo del. Results: Two hours after intraportal injection of lipopolysacchar ide (5 mg/kg in 10 min) the rats were randomly treated and received a bolus dose of N-G-nitro-L-arginine methyl ester (10 mg/kg, n=7), amino ethylisothiourea (10 mg/kg, n=6) or normal saline, (n=7), After 1 h, N -G-nitro-L-arginine methyl ester blockade yielded a higher rate of non -perfused sinusoids than normal saline (27+/-2% vs 19+/-5%, p<0.05), L PS-induced leukocyte stagnation in sinusoids was further increased (p< 0.05) in all groups after 1 h treatment, but N-G-nitro-L-arginine meth yl ester clearly accentuated leukocyte accumulation in sinusoids as co mpared to normal saline (69+/-19% vs 16+/-4%, p<0.05), Both modalities of nitric oxide blockade elicited a significant enhancement in the nu mber of leukocytes adherent to the postsinusoidal venules in contrast to normal saline (N-G-nitro-L-arginine methyl ester 48+/-17%, aminoeth yl-isothiourea 33+/-9% vs normal saline 1+/-5%, p<0.05). Conclusions: We conclude that complete nitric oxide blockade aggravates lipopolysac charide-induced hepatic microvascular perfusion failure and enhances l eukocyte accumulation, in both sinusoids and postsinusoidal venules, T he preferential inducible nitric oxide synthase inhibitor aminoethyl-i sothiourea has a moderate negative effect, favoring leukocyte adhesion in postsinusoidal venules, and its usefulness demands further researc h, especially concerning its late effects.