INVOLVEMENT OF NITROXYL (HNO) IN THE CYANAMIDE-INDUCED VASORELAXATION OF RABBIT AORTA

被引：27

作者：

FUKUTO, JM

GULATI, P

NAGASAWA, HT

机构：

[1] UNIV MINNESOTA,MINNEAPOLIS,MN 55417

[2] VET ADM MED CTR,MED RES LABS,MINNEAPOLIS,MN 55417

来源：

BIOCHEMICAL PHARMACOLOGY | 1994年 / 47卷 / 05期

关键词：

NITROXYL; CYANAMIDE; VASORELAXATION; CATALASE; ALDEHYDE DEHYDROGENASE; CGMP;

D O I：

10.1016/0006-2952(94)90495-2

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Relaxation of precontracted rabbit aortic rings in vitro by cyanamide, a clinically used alcohol deterrent drug, required catalase and H2O2, suggesting that a bioactivation mechanism was involved. Since the oxidation of cyanamide by catalase/H2O2 had been shown previously to lead to nitroxyl (HNO) generation via the intermediate N-hydroxycyanamide, and aortic ring relaxation was inhibited by the catalase inhibitor, 3-aminotriazole, HNO appears to be responsible for the vasorelaxation mediated by cyanamide. This was further supported by the observation that N,O-dibenzoyl-N-hydroxycyanamide (DBHC), a derivative of N-hydroxycyanamide that releases HNO in the absence of catalase/H2O2, was a potent vasorelaxant, with an EC(50) of 4.2 +/- 1.3 x 10(-6) M.

引用

收藏

页码：922 / 924

页数：3

相关论文

共 13 条

[1] INHIBITION OF ALDEHYDE DEHYDROGENASE IN BRAIN AND LIVER BY CYANAMIDE [J].

DEITRICH, RA ;

TROXELL, PA ;

WORTH, WS ;

ERWIN, VG .

BIOCHEMICAL PHARMACOLOGY, 1976, 25 (24) :2733-2737

[2] THE METABOLIC-ACTIVATION OF CYANAMIDE TO AN INHIBITOR OF ALDEHYDE DEHYDROGENASE IS CATALYZED BY CATALASE [J].

DEMASTER, EG ;

SHIROTA, FN ;

NAGASAWA, HT .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 122 (01) :358-365

[3] METABOLIC-ACTIVATION OF CYANAMIDE BY LIVER-MITOCHONDRIA, A REQUIREMENT FOR THE INHIBITION OF ALDEHYDE DEHYDROGENASE ENZYMES [J].

DEMASTER, EG ;

KAPLAN, E ;

SHIROTA, FN ;

NAGASAWA, HT .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1982, 107 (04) :1333-1339

[4]

FUKUTO JM, 1992, J PHARMACOL EXP THER, V263, P546

[5] N,O-DIACYLATED-N-HYDROXYARYLSULFONAMIDES - NITROXYL PRECURSORS WITH POTENT SMOOTH-MUSCLE RELAXANT PROPERTIES [J].

FUKUTO, JM ;

HSZIEH, R ;

GULATI, P ;

CHIANG, KT ;

NAGASAWA, HT .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 187 (03) :1367-1373

[6] PRODRUGS OF NITROXYL AS INHIBITORS OF ALDEHYDE DEHYDROGENASE [J].

LEE, MJC ;

NAGASAWA, HT ;

ELBERLING, JA ;

DEMASTER, EG .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (20) :3648-3652

[7] N1-HYDROXYLATED DERIVATIVES OF CHLORPROPAMIDE AND ITS ANALOGS AS INHIBITORS OF ALDEHYDE DEHYDROGENASE INVIVO [J].

LEE, MJC ;

ELBERLING, JA ;

NAGASAWA, HT .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (20) :3641-3647

[8] INHIBITION OF HEPATIC ALDEHYDE DEHYDROGENASES IN THE RAT BY CALCIUM CARBIMIDE (CALCIUM CYANAMIDE) [J].

LOOMIS, CW ;

BRIEN, JF .

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1983, 61 (09) :1025-1034

[9] AN N-HYDROXYLATED DERIVATIVE OF CYANAMIDE THAT INHIBITS YEAST ALDEHYDE DEHYDROGENASE [J].

NAGASAWA, HT ;

LEE, MJC ;

KWON, CH ;

SHIROTA, FN ;

DEMASTER, EG .

ALCOHOL, 1992, 9 (05) :349-353

[10]

NAGASAWA HT, 1990, J MED CHEM, V33, P3122