Antihypertensive effects of captopril in combination with diuretics in spontaneously hypertensive rats

To examine the antihypertensive effects of captopril, when used in combination with diuretics, an oral dose of the agent (30 mg/kg) was given to spontaneously hypertensive rats pretreated for 1 week with trichlormethiazide (TCTZ), hydrochlorothiazide (HCTZ), furosemide, or water. One-week treatment with diuretics did not lower blood pressure, but potentiated the anti-hypertensive action of captopril in magnitude as well as duration. The degree of potentiation was in the following order: furosemide greater than or equal to HCTZ greater than TCTZ. Plasma renin concentration (PRC) prior to the administration of captopril was highest in the furosemide group, followed by the HCTZ, TCTZ, and control groups, in this order. When data from four groups were taken together, the reduction of blood pressure following captopril administration was closely related to PRC before administration. These data suggest that repeated administration of diuretics renders the maintenance of blood pressure more dependent on the renin-angiotensin system without affecting blood pressure and that this situation underlies the potentiation of the antihypertensive action of captopril by combined use of diuretics. There was no qualitative difference between furosemide and thiazides in the potentiation of anti-hypertensive action of captopril.