1. 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.
2. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment.
3. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats.
4. 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.
5. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group.
6. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage.
7. 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.
8. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium.
9. 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.