CARBON-MONOXIDE DOES NOT INHIBIT GLYCERYL TRINITRATE BIOTRANSFORMATION BY OR RELAXATION OF AORTA

被引:13
作者
LIU, ZG [1 ]
BRIEN, JF [1 ]
MARKS, GS [1 ]
MCLAUGHLIN, BE [1 ]
NAKATSU, K [1 ]
机构
[1] QUEENS UNIV,DEPT PHARMACOL & TOXICOL,KINGSTON K7L 3N6,ONTARIO,CANADA
关键词
GLYCERYL TRINITRATE; BIOTRANSFORMATION; RABBIT AORTA; VASODILATATION; CARBON MONOXIDE (CO); HEMOPROTEIN;
D O I
10.1016/0014-2999(92)90275-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Carbon monoxide (CO) was employed to assess the role of ferrous hemoproteins in the vasodilation and biotransformation of glyceryl trinitrate (GTN) in rabbit aortic strips. These tissues were contracted submaximally with phenylephrine, exposed to CO for 5 min, and then incubated with 0.5-mu-M [1,3-C-14]GTN in the presence of CO for 2 min or 30 s. The [C-14]GTN-induced relaxation of the strips was recorded, and [C-14]GTN biotransformation to [C-14]glyceryl dinitrate metabolities by the tissues was determined by thin-layer chromatographic-liquid scintillation spectrometric analysis. CO treatment inhibited neither GTN-induced relaxation nor GTN biotransformation to glyceryl dinitrate metabolites. These results indicate that ferrous hemoproteins are probably not involved in the biotransformation of GTN that is associated with relaxation of the rabbit aortic strips.
引用
收藏
页码:129 / 132
页数:4
相关论文
共 10 条
[1]  
BENNETT BM, 1986, J PHARMACOL EXP THER, V237, P629
[2]  
BRIEN JF, 1988, J PHARMACOL EXP THER, V244, P322
[3]  
IGNARRO LJ, 1981, J PHARMACOL EXP THER, V218, P739
[4]  
Jefcoate C.R., 1986, CYTOCHROME P 450 STR, P387
[5]   BIOTRANSFORMATION OF GLYCERYL TRINITRATE AND ELEVATION OF CYCLIC-GMP PRECEDE GLYCERYL TRINITRATE-INDUCED VASODILATION [J].
KAWAMOTO, JH ;
MCLAUGHLIN, BE ;
BRIEN, JF ;
MARKS, GS ;
NAKATSU, K .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1990, 15 (05) :714-719
[6]  
LAU DTW, 1989, BIOCHEM PHARMACOL, V38, P543
[7]   CYTOCHROME-P-450 MEDIATED BIOTRANSFORMATION OF ORGANIC NITRATES [J].
MCDONALD, BJ ;
BENNETT, BM .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1990, 68 (12) :1552-1557
[8]  
NEEDLEMAN P, 1965, MOL PHARMACOL, V1, P77
[9]   NITRIC-OXIDE FORMATION DURING MICROSOMAL HEPATIC DENITRATION OF GLYCERYL TRINITRATE - INVOLVEMENT OF CYTOCHROME-P-450 [J].
SERVENT, D ;
DELAFORGE, M ;
DUCROCQ, C ;
MANSUY, D ;
LENFANT, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 163 (03) :1210-1216
[10]   ANTAGONISM OF GLYCEROL TRINITRATE ACTIVITY BY AN INHIBITOR OF GLUTATHIONE S-TRANSFERASE [J].
YEATES, RA ;
SCHMID, M ;
LEITOLD, M .
BIOCHEMICAL PHARMACOLOGY, 1989, 38 (11) :1749-1753