Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals.
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), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(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.
Department of Medicine, University of Maryland School of Medicine, Baltimore.
D E
DE
Anderson
X J
XJ
Yuan
C M
CM
Tseng
L J
LJ
Rubin
G M
GM
Rosen
M L
ML
Tod
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology
D015220:Calcium Channels; D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; C029217:phenyl-N-tert-butylnitrone; D008469:Meclofenamic Acid; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D002374:Catalase; D013482:Superoxide Dismutase; D008751:Methylene Blue