EFFECT OF NORADRENALINE ON RADIOPROTECTTVE EFFECT OF CALCIUM CHANNEL BLOCKERS

摘要

Calcium channel blockers can be classified into three main subgroups on the basis of their pharmacologic features. In earlier work the radioprotective effect of dilthiazem and nifedipine was proved, when these antagonists were given to mice s.c. or i.p. In this work mechanism of radioprotective activity was studied. For indirect investigation of the cardiovascular effects leading to hypoxia in mice, measurements of rectal temperature were used with assumption that hypothermic response reflects hypometabolic effects which are considered as compensatory reaction of the organism to hypoxia. I.p. administration of Diacordin (diltiazem hydrochlorid, Le-civa, Praha) in the doses of 25-100 mg/kg to mice led to a significant decrease rectal temperature at the interval of 15 minutes to 2 hours after injection. This decrease was influenced by Noradrenaline administration. The dose of 2.8 mg/kg was optimal for significant inhibition of the hypothermic response first hour after administration of Diacordin. Administration of Noradrenaline before Diacordin reduced radioprotective effect of Diacordin. We studied radioprotective effect on: 1. survival of lethal irradiated mice 2. hematological indicators (number of CFU-S, CFU-GM in the bone marrow and the spleen). Our experiment suported hypothesis that radioprotective activity of Diacordin is induced by at least two mechanisms. These two mechanisms are: 3. protection by means of hypoxia as a result of the effect of treatment on cardiovascular system 4. inhibition of the influx of Ca~(2+) through specialized channels into cells. Abbreviations: CFU-GM - colony-forming unit-granulocyte/macrophage, CFU-S -colony-forming unit-spleen, E-CFU-S - endogenous colony-forming unit-spleen, Di -Diacordin, Na - Noradrenaline, Di + Na Diacordin and Noradrenaline, C- nonirradiated group.