Superoxide anion scavengers restore NO-mediated pulmonary vasodilation after lung transplantation

Left lung autotransplantation (LLA) results in a chronic attenuation in end othelium-dependent, nitric oxide (NO)-mediated pulmonary vasodilation. We t ested the hypothesis that this abnormality involves a decrease in the effec tive concentration of NO due to inactivation by superoxide anion. Size- and position-matched pulmonary arterial rings were isolated from the right (co ntrol) and left (LLA) lungs of seven dogs 1-5 mo post-LLA. The rings were s uspended for isometric tension recording and contracted with phenylephrine, and cumulative dose-response curves for ACh or calcium ionophore (A-23187) were generated. Endothelium-dependent relaxation to ACh was inhibited post -LLA, with the maximum vasorelaxation response reduced from 88 +/- 5 to 63 +/- 5% (P < 0.01) post-LLA. In contrast, after pretreatment with the supero xide anion scavengers tiron or superoxide dismutase (SOD), the dose-respons e relationships for ACh were similar in control and LLA rings. Oxypurinol, which inhibits superoxide anion production by endothelial xanthine oxidase, also restored the vasorelaxation response to ACh in LLA rings. The pulmona ry vasorelaxant response to A-23187 was also attenuated (P < 0.01) post-LLA , and this effect was entirely reversed by pretreatment with tiron, SOD, or oxypurinol. These results indicate that the attenuated responses to these pulmonary vasorelaxants post-LLA involve inactivation of NO by superoxide a nion generated by endothelial xanthine oxidase.