Tolerance induction by transdermal glyceryl trinitrate in rats

被引：19

作者：

De la Lande, IS ^{[1
]}

Stafford, I ^{[1
]}

Horowitz, JD ^{[1
]}

机构：

[1] Univ Adelaide, Cardiol Unit, NW Adelaide Hlth Serv, Woodville, SA 5011, Australia

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1999年 / 374卷 / 01期

基金：

英国医学研究理事会;

关键词：

aorta; rat; tolerance induction; vascular relaxation; glyceryl trinitrate; acetylcholine; sodium nitroprusside;

D O I：

10.1016/S0014-2999(99)00319-2

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Mechanisms of mild glyceryl trinitrate tolerance in rats (transdermal application; 15 mg/day/2 days) were examined in isolated aortic rings contracted with phenylephrine. Tolerance to glyceryl trinitrate was comparable in both endothelium-intact and -denuded vessels; the maximum relaxation decreased to 70-80% and the EC50 increased 3-4-fold. There was minimal cross-tolerance to acetylcholine (1.7-fold increase in EC50) and none to sodium nitroprusside. The results suggest that mild tolerance to glyceryl trinitrate in rats is mediated by mechanisms which are predominantly endothelium-independent and which produce little activation of the cellular mechanism responsible for cross-tolerance. (C) 1999 Elsevier Science B.V. All rights reserved.

引用

页码：71 / 75

页数：5

共 15 条

[1]

BRIEN JF, 1986, J PHARMACOL EXP THER, V237, P608

[2] Nitroglycerin tolerance at the platelet level in patients with angina pectoris [J].

Chirkov, YY ;

Chirkova, LP ;

Horowitz, JD .

AMERICAN JOURNAL OF CARDIOLOGY, 1997, 80 (02) :128-131

[3] Effects of guanylyl cyclase and protein kinase G inhibitors on vasodilatation in non-tolerant and tolerant bovine coronary arteries [J].

De la Lande, IS ;

Stafford, I ;

Horowitz, JD .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 370 (01) :39-46

[4] EFFECT OF TOLERANCE TO GLYCERYL TRINITRATE ON VASCULAR-RESPONSES IN CONSCIOUS RABBITS [J].

DU, ZY ;

DUSTING, GJ ;

WOODMAN, OL .

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1991, 18 (06) :439-447

[5]

DU ZY, 1992, J THORAC CARDIOV SUR, V104, P1280

[6] NITROGLYCERIN-INDUCED DIRECT PROTECTION OF THE ISCHEMIC MYOCARDIUM IN ISOLATED WORKING HEARTS OF RATS WITH VASCULAR TOLERANCE TO NITROGLYCERIN [J].

FERDINANDY, P ;

SZILVASSY, Z ;

CSONT, T ;

CSONKA, C ;

NAGY, E ;

KOLTAI, M ;

DUX, L .

BRITISH JOURNAL OF PHARMACOLOGY, 1995, 115 (07) :1129-1131

[7]

HENRY PJ, 1989, J PHARMACOL EXP THER, V248, P762

[8]

KUKOVETZ WR, 1990, EUR J CLIN PHARM S1, V38, P9

[9] In vivo nitrate tolerance is not associated with reduced bioconversion of nitroglycerin to nitric oxide [J].

Laursen, JB ;

Mulsch, A ;

Boesgaard, S ;

Mordvintcev, P ;

Trautner, S ;

Gruhn, N ;

NielsenKudsk, JE ;

Busse, R ;

Aldershvile, J .

CIRCULATION, 1996, 94 (09) :2241-2247

[10] Effect of selective inhibition of soluble guanylyl cyclase on the KCa channel activity in coronary artery smooth muscle [J].

Li, PL ;

Jin, MW ;

Campbell, WB .

HYPERTENSION, 1998, 31 (01) :303-308

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