TY - JOUR
T1 - Nitrone Spin-Traps Block Calcium Channels and Induce Pulmonary Artery Relaxation Independent of Free Radicals
AU - Anderson, Daniel E.
AU - Yuan, Xiao Jian
AU - Tseng, Chun Ming
AU - Rubin, Lewis J.
AU - Rosen, Gerald M.
AU - Tod, Mary L.
PY - 1993/6/30
Y1 - 1993/6/30
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1993.1707
DO - 10.1006/bbrc.1993.1707
M3 - Article
C2 - 8391809
AN - SCOPUS:0027172051
VL - 193
SP - 878
EP - 885
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -