Interaction of ACE inhibitors and AT1-receptor blockers on maximum blood pressure response in spontaneous hypertensive rats

Abstract

This study in spontaneous hypertensive rats (SHR) was designed to determine whether a greater fall in blood pressure (BP) could be achieved with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and an AT1-receptor blocking drug than with higher doses of either drug alone. The peak effect of captopril occurred 3—4 hours post-dose and a plateau response was achieved with 10 mg/kg. The peak effect of losartan occurred 7—8 hours post-dose and a plateau response was achieved with 10 mg/kg. Increasing the dose of either drug caused no greater fall in BP, but increased the duration of the effect. Captopril, 10 mg/kg, administered with losartan 10 mg/kg caused a greater fall in BP than captopril or losartan, 20 mg/kg. This was present after acute doses or after one week of daily therapy. The combination of ACE-I and AT1-blocking drugs is more effective than either therapy alone and may be a useful combination to manage hypertension and/or cardiac failure.