氢氯噻嗪的利尿与抗利尿作用致大鼠尿量及组织含水量的变化

目的:探讨药物氢氯噻嗪对健康机体的利尿作用与抗利尿作用间的规律关系。方法:对应用氢氯噻嗪健康大鼠组和无药对照鼠组,分别采用自由饮水、少量清水灌胃(4 h:125 mL.kg-1)、和较大量清水灌胃(4 h:175 mL.kg-1)及超量清水灌胃(4 h:260 mL.kg-1)的"清水利尿"条件时,观察给水量不同条件时大鼠6 h尿量的变化,及超量水灌胃后大鼠血浆渗透压、脑组织含水量及肾组织病理切片水肿情况。结果:自由饮水和少量水灌胃条件时,用药鼠的6 h尿量多于未用药鼠(P<0.01);在较多水灌胃和超量水灌胃条件时,用药鼠的6 h尿量少于未用药鼠(P<0.01);在超量水灌胃(4 h:260 mL.kg-1)后,用药鼠血浆渗透压比未用药鼠低,而用药鼠脑组织含水量比未用药组鼠多(P<0.01),用药组鼠肾组织病理切片出现明显的水肿,未用药组鼠无明显水肿。结论:氢氯噻嗪本身具有利尿作用与抗利尿作用并存,即当尿量不多时显现出利尿效应,当尿量过多(如水利尿)时显现出抗利尿效应;且若进入机体水量过多,该药可致水中毒。

Diuretic and anti-diuretic effects of hydrochlorothiazide on urine volume and tissue water content

Objective： To explore diuretic and relative anti-diuretic effect of hydrochlorothiazide on various water intake patterns.Methods： Rats were randomly divided into hydrochlorothiazide administration group（group A） and non-administration group（group B）.Two rats were raised in one metabolic cage,and six cages were comprised in each group.Free water intake（feeding,p.o.）,controlled water intake with low volume（intragastric administration with 125 mL/kg in 4hrs,i.g.125）,medium volume（175 mL/kg in 4 hrs,i.g.175） and excessive water intake（260 mL/kg in 4 hrs,i.g.260） were employed to each group（group A and B,respectively）.In first round,quantities of urine volume in the first 6 hrs（Vol6）,plasma osmolality（Posmol） and cerebral tissue content of water（CH2O） were calculated by hydrochlorothiazide administration for 3 days（or placebo） in groups.Controlled water intake with i.g.175 and i.g.260 were employed in the second and the third round in group A and B,Vol6 and CH2O were calculated,respectively.Results： A significantly high urine volumes in the first 6 hrs were observed in group A（P0.01） from p.o.and i.g.125 rats,but significantly low in i.g.175 and i.g.260 rats（P0.01）.It showed the lower plasma osmolality level in group A i.g.260 rats,while the cerebral tissue content of water were significantly high（P0.01）.A clearly histological edema changes could be found in group A i.g.260 rats.Conclusions： Hydrochlorothiazide has diuretic and anti-diuretic effects.Functional shift from diuresis to antidiuresis is depending on urine formation,which means diuretic effect combined with low urine formation,while antidiuresis effect combines with high urine formation.It is demonstrated that hydrochlorothiazide administration has the risk to water intoxication under the excessive water intake condition.