N-Acetyl-L-Cysteine Mitigates Aortic Tone Injury Following Liver Ischemia-Reperfusion

Liver ischemia and subsequent reperfusion (IR) are associated with secondary, remote organ reperfusion injury attributable to oxidative stress mediators. Because N-acetyl-L-cysteine (NAC) was effective in attenuating lung reperfusion injury, its properties on aortic dysfunction were tested. Rat isolated perfused aortic rings (n = 8/group) were evaluated during and after exposure to liver postischemia perfusate. Aortic response to phenylephrine under these conditions was also assessed in the presence or absence of increasing concentrations of NAC. Aortic rings incubated with postischemia perfusates exhibited abnormally protracted contraction. Their response to phenylephrine was reduced to 18 +/- 7% and 65 +/- 11% of controls during and after the exposure, respectively, and their subsequent relaxation was irregular. NAC 0.25 mM best attenuated the IR-induced aortic tone impairments, 0.12 mM affected it slightly, and IR-NAC 0.5 mM and IR-NAC 0.74 mM solutions dilated the rings proportionately, abolishing reactions to both IR solutions and phenylephrine. Xanthine oxidase activity and reduced glutathione (GSH) level in all IR ring tissues were inversely proportionate, but not directly so. Thus, liver IR impaired aortic tone and its response to phenylephrine, even after removal of toxic elements. NAC concentrations directly and inversely correlated with xanthine oxidase activity but not with GSH level. It preserved aortic functions dose-specifically, mainly by oxidant quenching.