Biamino G, Wessel H J, Nöring J, Schröder R
Int J Clin Pharmacol Biopharm. 1975 Oct;12(3):356-68.
The beneficial effect of furosemide in treatment of chronic and particularly of acute congestive heart failure has been attributed to its potent diuretic action. In recent studies [16], it has been postulated that the effect of this diuretic agent is primarily vascular in origin. The results of venous occlusion plethysmographic experiments (modificated Whitney-gauge technique) carried out in this study on the forearm of 6 healthy men, show that furosemide (40 mg. i.v.) does not influence arterial blood flow (4-5 ml/100 ml tissue - min). In contrast furosemide induces a prompt significant (p less than 0.001) and sustained (about 45 min) increase in venous capacitance (deltaV/100 ml tissue = 15%) and a corresponding decrease in E'. The direct effect of furosemide on vascular muscle tone was studied in vitro on portal vein and aortic strip preparations from 76 male rats. In 18 experiments mechanical and electrical activity (using three pressure electrodes) were simultaneously recorded. The results of the in vitro experiments show: 1. Only extremely high furosemide concentrations (greater than 500 mg/l) induce slight relaxation of aortic strips. 2. Furosemide causes in contrast a marked dose-dependent per cent decrease of the integrated isometric tension in portal vein preparations: 14 mg/l reduce the initial tension (= 100%) to 80%; 35 mg/l to 65%; 70 mg/l to 50% and 100 mg/l to 35%. 3. The venodilating furosemide effect is significantly (p less than 0.001) increased by reduction in external Na+-concentration [Na+]0 to 120 mM though further reduction in the [Na+]0 to 90 mM does not cause additional changes in the relaxation slope. 4. The simultaneous records of electrical activity demonstrate that the relaxing effect of furosemide is based on decreased spike frequency in shortened bursts as well as on pronounced impairment of conduction velocity without relevant changes in pacemaker frequency. These in vitro results are discussed from the point of view that a furosemide induced decrease in Na+-permeability may determine the changes obtained in electrical and mechanical behaviour of portal veins of the rat.
速尿在治疗慢性尤其是急性充血性心力衰竭方面的有益作用一直归因于其强大的利尿作用。在最近的研究[16]中,有人推测这种利尿剂的作用主要源于血管。本研究对6名健康男性的前臂进行静脉闭塞体积描记实验(改良惠特尼测量技术)的结果表明,速尿(静脉注射40毫克)不影响动脉血流量(4 - 5毫升/100毫升组织 - 分钟)。相反,速尿可使静脉容量迅速显著增加(p小于0.001)并持续(约45分钟)(ΔV/100毫升组织 = 15%),同时E'相应降低。在体外对76只雄性大鼠的门静脉和主动脉条制备物研究了速尿对血管肌张力的直接作用。在18个实验中同时记录了机械和电活动(使用三个压力电极)。体外实验结果表明:1. 只有极高的速尿浓度(大于500毫克/升)会使主动脉条轻微松弛。2. 相反,速尿会使门静脉制备物中的等长张力积分显著剂量依赖性降低:14毫克/升将初始张力(= 100%)降至80%;35毫克/升降至65%;70毫克/升降至50%,100毫克/升降至35%。3. 通过将外部Na⁺浓度[Na⁺]₀降至120毫摩尔,速尿的静脉舒张作用显著增强(p小于0.001),尽管将[Na⁺]₀进一步降至90毫摩尔不会使舒张斜率产生额外变化。4. 电活动的同步记录表明,速尿的舒张作用基于缩短的爆发中动作电位频率降低以及传导速度明显受损,而起搏频率无相关变化。从速尿诱导的Na⁺通透性降低可能决定大鼠门静脉电和机械行为变化这一角度对这些体外实验结果进行了讨论。