慢性口服硝酸异山梨酯对大鼠动脉平滑肌体外收缩性的影响。

Effects of chronic oral administration of isosorbide dinitrate on in vitro contractility of rat arterial smooth muscle.

作者信息

Trongvanichnam K, Mitsui-Saito M, Ozaki H, Karaki H

机构信息

Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Japan.

出版信息

Jpn J Pharmacol. 1996 Jun;71(2):167-73. doi: 10.1254/jjp.71.167.

DOI:10.1254/jjp.71.167

PMID:8835643

Abstract

In this study, we examined the effects of in vitro and in vivo treatment with isosorbide dinitrate (ISDN) on the in vitro response of isolated rat aorta. The in vitro treatment of isolated aorta with ISDN (100 microM) for 2 hr had no effect on the ISDN-induced relaxation of norepinephrine-induced contraction. In the aorta isolated from the rats treated with a high dose (90 mg/kg) of ISDN for 7-14 days, in contrast, the relaxant effect of ISDN was significantly reduced. However, the relaxant effect of sodium nitroprusside was only slightly attenuated by the treatment with a high dose of ISDN for 14 days; and the relaxant effects of 8-bromo-cGMP, levcromakalim and verapamil were unchanged. These results suggest that tolerance to ISDN was obtained only after the in vivo chronic treatment with a high dose of ISDN. ISDN may desensitize the nitric oxide-generating step rather than inactivate guanylate cyclase or the downstream pathways.

摘要

在本研究中，我们检测了硝酸异山梨酯（ISDN）体外及体内处理对离体大鼠主动脉体外反应的影响。用ISDN（100 microM）对离体主动脉进行2小时的体外处理，对ISDN诱导的去甲肾上腺素诱导收缩的舒张作用没有影响。相比之下，在从接受高剂量（90 mg/kg）ISDN处理7 - 14天的大鼠分离出的主动脉中，ISDN的舒张作用显著降低。然而，硝普钠的舒张作用仅在高剂量ISDN处理14天时略有减弱；8-溴-cGMP、左卡尼汀和维拉帕米的舒张作用未改变。这些结果表明，只有在高剂量ISDN体内长期处理后才会产生对ISDN的耐受性。ISDN可能使一氧化氮生成步骤脱敏，而不是使鸟苷酸环化酶或下游途径失活。