Prevention of the development of spontaneous hypertension in rats by captopril (SQ 14,225).

Indirect systolic blood pressure (SBP) was monitored in male, weanling, spontaneously hypertensive rats (SHR) maintained on water for 16 weeks (group A) or on captopril therapy (100 mg/kg/day in drinking water) for 4 (group B), 8 (group C), 12 (group D), 16 (group E) weeks. Weanling SHR of group A developed typical, time-related hypertension over a 16-week observation period. In marked contrast, SHR receiving captopril did not develop hypertension. Discontinuation of captopril after 4, 8, 12 or 16 weeks resulted in the usual development of hypertension. There was a transient increase in water consumption of drug treated rats which returned to normal by 8 weeks of dosing. Conversely, when captopril therapy was discontinued after 4, 8 or 12 weeks, there was a transient decrease in water intake, the magnitude of which was inversely related to the duration of drug therapy. These results demonstrate that daily captopril therapy was able to completely prevent the development of spontaneous hypertension. Explanations for the mechanism(s) underlying the influence of captopril on blood pressure and water intake remain speculative.