Manhem P J, Clark S A, Brown W B, Murray G D, Robertson J I
Clin Sci (Lond). 1985 Nov;69(5):511-5. doi: 10.1042/cs0690511.
Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.
每天通过灌胃给予自发性高血压大鼠氯噻嗪（100毫克/千克体重），持续4周。另一组自发性高血压大鼠仅给予自来水作为对照。在治疗前2周和治疗期间4周测量总可交换钠、血压和体重。治疗前，两组大鼠的可交换钠、血压和体重相似。氯噻嗪显著减轻了自发性高血压大鼠的血压升高，这种作用在治疗的前2.5周最为明显，此后作用减弱。氯噻嗪治疗组的大鼠体重增加比对照组慢。以毫摩尔/千克体重表示的可交换钠在任何阶段两组之间均无显著差异。当以毫摩尔/大鼠表示可交换钠时，氯噻嗪治疗的动物中可交换钠的升高更为缓慢，这与它们体重增加较慢一致。氯噻嗪的降压作用与可交换钠的变化之间没有时间关联。因此，虽然氯噻嗪治疗自发性高血压大鼠会减缓体重和可交换钠的增加，但该药物的降压作用显然是由其他机制介导的。
