Hepatic ischemia is associated with an increase in liver parenchyma nitric oxide that is in part enzyme-independent

Background: Nitric oxide (NO) might be involved in liver response to local ischemia-reperfusion injury. Methods: A specific NO-sensitive electrode was inserted into liver parenchyma of anesthetized rabbits. After a 45-min period of stable NO signal, the vascular pedicle of the caudal lobe of the liver was clamped for 45 min, then the clamp was removed. Perfusion of the right upper lobe was left unchanged. The same procedure was applied in other animals after administration of a long-acting nonspecific NO synthase inhibitor NAPNA. Results. Occlusion of the caudal pedicle was associated with a mean threefold increase In No signal measured in the caudal lobe. After unclamping, this signal returned within 8 min to baseline value and remained stable for the next 6 h. in the right upper lobe, NO signal was unaffected by caudal lobe ischemia. By the end of the 6-h reperfusion period, administration of the No inhibitor L-NAME led to a suppression of the NO signal, thus demonstrating the specificity of the measurement. Plasma nitrate and nitrite concentrations remained almost unchanged during the study period in all groups. in animals whose NO synthases had been previously inhibited by NAPNA, clamping the caudal pedicle for 45 min was still associated with a significant increase in caudal lobe NO signal. Conclusion: Nitric oxide is present in liver parenchyma, and its generation is dramatically affected by an ischemia injury. The increased NO generation during local ischemia is, at least in part, independent of NO synthases.