血管活性药物对无钙溶液中氟化物诱导的血管平滑肌收缩的影响。

Effects of vasoactive drugs on fluoride-induced contractions of vascular smooth muscle in calcium-free solution.

作者信息

Nguyen-Duong H

出版信息

Arzneimittelforschung. 1985;35(8):1246-50.

Abstract

Cumulative dose-response curves were obtained for contractions induced by fluoride in bovine facial veins and arteries in the presence and absence of external Ca (Cao). In 1.4 mmol/l Cao the threshold for contractions was lower for veins than for the arteries, i.e. at 1 mmol/l vs. 2 mmol/l F-. After Ca withdrawal from the external medium, the ED50 values for veins and arteries were shifted from 2.2 to 10 and from 4.5 and 8.5 mmol/l F-, respectively. Several vasodilators (order of potency to relax veins: caffeine less than verapamil less than sulmazole less than sodium nitroprusside less than papaverine) were investigated for their ability to inhibit contractions induced by F- in Ca2+-free solution. None of them was able to counteract F- induced contractions in Ca2+-free solutions. Furosemide and beta-methyldigoxine were also ineffective. However, nitroprusside, sulmazole and papaverine were able to relax strips pretreated with Ca2+-free solutions. By contrast, contractions of depolarized veins induced by F- in Ca2+-free solutions were significantly, though transiently, inhibited by 10 mmol/l ammonium ions. The vasodilators tested in this study seem thus to act by inhibiting Ca influx at some level of the membrane, while F- may act by mobilizing Ca ions from some unidentified, cellular pools not accessible to the drugs tested in this study.

摘要

在有和没有细胞外钙（Caₒ）的情况下，获得了氟化物诱导牛面部静脉和动脉收缩的累积剂量反应曲线。在1.4 mmol/L Caₒ时，静脉收缩的阈值低于动脉，即分别为1 mmol/L氟化物时静脉收缩，2 mmol/L氟化物时动脉收缩。从细胞外培养基中去除钙后，静脉和动脉的半数有效剂量（ED50）值分别从2.2 mmol/L氟化物变为10 mmol/L氟化物，从4.5 mmol/L氟化物变为8.5 mmol/L氟化物。研究了几种血管舒张剂（舒张静脉效力顺序：咖啡因＜维拉帕米＜舒马唑＜硝普钠＜罂粟碱）在无钙溶液中抑制氟化物诱导收缩的能力。它们中没有一种能够抵消无钙溶液中氟化物诱导的收缩。呋塞米和β-甲基地高辛也无效。然而，硝普钠、舒马唑和罂粟碱能够使经无钙溶液预处理的条带舒张。相比之下，无钙溶液中氟化物诱导的去极化静脉收缩被10 mmol/L铵离子显著但短暂地抑制。因此，本研究中测试的血管舒张剂似乎是通过在膜的某个水平抑制钙内流起作用，而氟化物可能是通过从本研究中测试的药物无法进入的一些未明确的细胞内钙库中动员钙离子起作用。