S-亚硝基硫醇对牛离体冠状动脉中三硝酸甘油耐受性的调节作用

S-nitrosothiol modulation of tolerance to glyceryl trinitrate in bovine isolated coronary artery.

作者信息

Zhang C L, De la Lande I S, Stafford I, Horowitz J D

机构信息

Cardiology Unit, Queen Elizabeth Hospital, University of Adelaide, Woodville, Australia.

出版信息

Eur J Pharmacol. 1994 Feb 11;252(3):299-304. doi: 10.1016/0014-2999(94)90176-7.

DOI:10.1016/0014-2999(94)90176-7

PMID:8162952

Abstract

The aim of the study was to ascertain whether induction of tolerance to glyceryl trinitrate (GTN) was modified by nitrosothiols. Vasodilator responses to GTN and to two nitrosothiols, namely S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-N-acetylcaptopril (SNOCAP) were measured in bovine coronary artery rings constricted with the thromboxane mimetic agent U46619. Pre-exposure of vessels to SNAP (10 microM) for 1 h resulted in cross-tolerance to GTN comparable with tolerance induced by GTN (1.0 microM). Tolerance was increased after pre-exposure to both agents. SNAP alone in lower concentrations (0.01, 0.1 and 1.0 microM) did not produce cross tolerance to GTN, but in combination with GTN (1.0 microM) caused a small but significant decrease in tolerance to GTN. This attenuating effect of SNAP on GTN tolerance was reproduced by SNOCAP (0.01 microM). We conclude that the nitrosothiols exert a biphasic effect on induction of tolerance to GTN.

摘要

本研究的目的是确定亚硝基硫醇是否会改变对硝酸甘油（GTN）的耐受性诱导。在用血栓素模拟剂U46619收缩的牛冠状动脉环中，测量了对GTN以及两种亚硝基硫醇（即S-亚硝基-N-乙酰青霉胺（SNAP）和S-亚硝基-N-乙酰卡托普利（SNOCAP））的血管舒张反应。将血管预先暴露于SNAP（10 microM）1小时会导致对GTN产生交叉耐受性，与GTN（1.0 microM）诱导的耐受性相当。预先暴露于两种药物后，耐受性增强。单独使用较低浓度（0.01、0.1和1.0 microM）的SNAP不会产生对GTN的交叉耐受性，但与GTN（1.0 microM）联合使用会导致对GTN的耐受性出现小幅度但显著的降低。SNOCAP（0.01 microM）重现了SNAP对GTN耐受性的这种减弱作用。我们得出结论，亚硝基硫醇对GTN耐受性的诱导具有双相作用。