Nitrone Spin-Traps Block Calcium Channels and Induce Pulmonary Artery Relaxation Independent of Free Radicals

Daniel E. Anderson, Xiao Jian Yuan, Chun Ming Tseng, Lewis J. Rubin, Gerald M. Rosen, Mary L. Tod

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), α-phenyl-tert-butylnitrone (PBN), and α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.

Original languageEnglish (US)
Pages (from-to)878-885
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume193
Issue number3
DOIs
StatePublished - Jun 30 1993

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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