NITRONE SPIN-TRAPS BLOCK CALCIUM CHANNELS AND INDUCE PULMONARY-ARTERY RELAXATION INDEPENDENT OF FREE-RADICALS

被引:44
作者
ANDERSON, DE
YUAN, XJ
TSENG, CM
RUBIN, LJ
ROSEN, GM
TOD, ML
机构
[1] UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201
[2] UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201
[3] UNIV MARYLAND,SCH PHARM,DEPT PHARMACOL & TOXICOL,BALTIMORE,MD 21201
[4] VET ADM MED CTR,BALTIMORE,MD 21218
关键词
D O I
10.1006/bbrc.1993.1707
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. © 1993 Academic Press, Inc.
引用
收藏
页码:878 / 885
页数:8
相关论文
共 22 条