Long-Term Efficacy of Captopril (SQ 14,225) In 2-Kidney Renal Hypertensive Rats

The effects of daily captopril therapy (30 mg/kg p.o.) given for one year on systolic blood pressure, heart rate and survival of 2-kidney renal hypertensive rats (2K-RHR) were examined. Captopril caused significant and sustained reductions in systolic blood pressure of 2K-RHR throughout the 1-year period with no important changes in heart rate. Simultaneous administration of the diuretic hydrochlorothiazide (HCTZ) enhanced the antihypertensive effect of captopril but did not normalize blood pressure, this despite no effect on blood pressure by HCTZ given alone. On the other hand, co-administration of guanethidine with captopril normalized blood pressure. Survival rates of 2K-RHR were highest in the rats receiving captopril plus HCTZ, next highest in rats receiving captopril alone and lowest in rats receiving water or HCTZ. The results demonstrate the long-term efficacy of captopril and suggest a sympathetic component in the maintenance of chronic 2-kidney renal hypertension.