Recombinant human superoxide dismutase enhances the effect of inhaled nitric oxide in persistent pulmonary hypertension

Robin H Steinhorn, George Albert, Daniel D. Swartz, James A. Russell, Carolyn R. Levine, Jonathan M. Davis

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

We investigated the pulmonary vascular effects of superoxide dismutase (SOD) alone and in combination with inhaled nitric oxide (iNO) in newborn lambs with persistent pulmonary hypertension (PPHN) following prenatal ligation of the ductus arteriosus. In in vitro experiments, pretreatment with SOD significantly enhanced vascular relaxation in response to the NO donor S-nitrosyl-acetylpenicillamine (SNAP) in fifth-generation pulmonary arteries isolated from lambs with PPHN. In vivo treatment of fully instrumented newborn lambs with a single intratracheal dose of recombinant human CuZn SOD (rhSOD; 5 mg/kg) produced selective dilation of the pulmonary circulation. Further studies, of the combination of rhSOD and iNO, showed enhancement of the pulmonary vascular effects of iNO after brief periods of inhalation of 5 ppm and 80 ppm NO. We conclude that rhSOD reduces pulmonary vascular resistance and facilitates the action of iNO in a lamb model of PPHN. This suggests that rhSOD may prove to be an effective adjunctive treatment for newborns with PPHN.

Original languageEnglish (US)
Pages (from-to)834-839
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume164
Issue number5
StatePublished - Sep 1 2001
Externally publishedYes

Keywords

  • Free radical scavengers
  • Lung
  • Newborn
  • Pulmonary artery

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Steinhorn, R. H., Albert, G., Swartz, D. D., Russell, J. A., Levine, C. R., & Davis, J. M. (2001). Recombinant human superoxide dismutase enhances the effect of inhaled nitric oxide in persistent pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine, 164(5), 834-839.