Interaction of ACE inhibitors and AT(1)-receptor blockers on maximum blood pressure response in spontaneous hypertensive rats.
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 AT(1)-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 AT(1)-blocking drugs is more effective than either therapy alone and may be a useful combination to manage hypertension and/or cardiac failure.
Morgan
Trefor
T
Department of Physiology, University of Melbourne, Parkville, Vic, Australia. t.morgan@physiology.unimelb.edu.au
Griffiths
Cory
C
Delbridge
Lea
L
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D013686:Telemetry
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D002216:Captopril; D019808:Losartan