Low doses of angiotensin converting enzyme inhibitors and angiotensin type 1 blockers have a synergistic effect but high doses are less than additive.
BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors and angiotensin type I (AT(1)) receptor blocking drugs block the effects of angiotensin II by different mechanisms. This study examined the effect of combination of different doses of the two drugs on blood pressure (BP).


METHODS
Blood pressure was measured by telemetry in spontaneous hypertensive rats (SHRs) and the acute response to losartan (L), captopril (C), or their combination in equal amounts was measured for doses of 0, 1.25, 2.5, 5, 10, 20, and 40 mg/kg.


RESULTS
The effect of the combination of low doses of the two drugs was more than additive (synergistic) with 80% of the full response achieved with L-2.5 + C-2.5. In higher doses the response was less than additive, but a greater decrease (P <.01) in systolic BP (44.6 +/- 2.5 mm Hg) was achieved with the combination than with captopril (37.1 +/- 2.7 mm Hg), which was greater (P <.05) than with losartan (32.9 +/- 2.4 mm Hg).


CONCLUSIONS
The interaction between ACE inhibitors and AT(1) blockers depends on the dose used, but the combination has greater BP-lowering effects than either drug as monotherapy.
Morgan
Trefor
T
Department of Physiology, University of Melbourne, Parkville, Victoria 3010, Australia. t.morgan@physiology.unimelb.edu.au
Griffiths
Cory
C
Delbridge
Lea
L
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002216:Captopril; D019808:Losartan