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Am J Physiol Heart Circ Physiol 276: H42-H46, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 1, H42-H46, January 1999

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

Sumihiko Seki1, Nicholas A. Flavahan2, Nicholas G. Smedira3, and Paul A. Murray1

1 Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, and 3 Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland 44195; and 2 Heart and Lung Institute, The Ohio State University, Columbus, Ohio 43210

Left lung autotransplantation (LLA) results in a chronic attenuation in endothelium-dependent, nitric oxide (NO)-mediated pulmonary vasodilation. We tested the hypothesis that this abnormality involves a decrease in the effective concentration of NO due to inactivation by superoxide anion. Size- and position-matched pulmonary arterial rings were isolated from the right (control) and left (LLA) lungs of seven dogs 1-5 mo post-LLA. The rings were suspended 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 superoxide anion scavengers tiron or superoxide dismutase (SOD), the dose-response 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 pulmonary 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 anion generated by endothelial xanthine oxidase.

pulmonary circulation; endothelium-dependent vasodilators; acetylcholine; calcium ionophore A-23187; superoxide dismutase; tiron; oxypurinol


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