Bioactivation of nitroglycerin - A new piece in the puzzle

被引：11

作者：

Mayer, B ^{[1
]}

机构：

[1] Inst Pharmakol & Toxikol, A-8010 Graz, Austria

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2003年 / 42卷 / 04期

关键词：

aldehyde dehydrogenase; nitrate metabolism; nitric oxide; vasodilation;

D O I：

10.1002/anie.200390124

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Even after more than a century it is not completely understood how nitroglycerin (GTN) functions in the treatment of ischemic heart disease (angina pectoris). Recent work by Jonathan Stamler and co-workers (Duke University) now suggests that bioactivation of nitroglycerin, which is essential to the vascular action of the drug, is catalyzed by mitochondrial aldehyde dehydrogenase (mtALDH; see scheme). These important findings are discussed with special emphasis given to their pharmacological and clinical implications.

引用

收藏

页码：388 / 391

页数：4

相关论文

共 24 条

[1] In vitro activation of soluble guanylyl cyclase and nitric oxide release: A comparison of NO donors and NO mimetics [J].

Artz, JD ;

Toader, V ;

Zavorin, SI ;

Bennett, BM ;

Thatcher, GRJ .

BIOCHEMISTRY, 2001, 40 (31) :9256-9264

[2] NITRATE TOLERANCE IN-VIVO IS NOT ASSOCIATED WITH DEPLETION OF ARTERIAL OR VENOUS THIOL LEVELS [J].

BOESGAARD, S ;

ALDERSHVILE, J ;

POULSEN, HE ;

LOFT, S ;

ANDERSON, ME ;

MEISTER, A .

CIRCULATION RESEARCH, 1994, 74 (01) :115-120

[3] Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase [J].

Brown, GC .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2001, 1504 (01) :46-57

[4]

Brunner F, 1996, J PHARMACOL EXP THER, V277, P48

[5] Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine [J].

Caramori, PRA ;

Adelman, AG ;

Azevedo, ER ;

Newton, GE ;

Parker, AB ;

Parker, JD .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1998, 32 (07) :1969-1974

[6] Identification of the enzymatic mechanism of nitroglycerin bioactivation [J].

Chen, ZQ ;

Zhang, J ;

Stamler, JS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (12) :8306-8311

[7]

FORSTER S, 1991, J CARDIOVASC PHARM, V17, P867

[8]

Gibbs WW, 1999, SCI AM, V280, P16

[9] Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance - A human in vivo study [J].

Gori, T ;

Burstein, JM ;

Ahmed, S ;

Miner, SES ;

Al-Hesayen, A ;

Kelly, S ;

Parker, JD .

CIRCULATION, 2001, 104 (10) :1119-1123

[10] Evidence supporting abnormalities in nitric oxide synthase function induced by nitroglycerin in humans [J].

Gori, T ;

Mak, SS ;

Kelly, S ;

Parker, JD .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2001, 38 (04) :1096-1101