SYNERGISTIC EFFECTS OF COMBINED CONVERTING-ENZYME INHIBITION AND ANGIOTENSIN-II ANTAGONISM ON BLOOD-PRESSURE IN CONSCIOUS TELEMETERED SPONTANEOUSLY HYPERTENSIVE RATS

Objective To investigate the chronic effects of combined administratio n of an angiotensin II receptor antagonist (valsartan) and an angioten sin converting enzyme inhibitor (benazeprilat) on blood pressure and h eart rate in conscious telemetered spontaneously hypertensive rats. Me thods Blood pressure and heart rate were monitored (by radiotelemetry) during 2-week infusions of 0.5-10 mg/kg valsartan per day and 0.5-10 mg/kg benazeprilat per day, alone or in combination, into conscious sp ontaneously hypertensive rats. Also, responses of blood pressure in co nscious spontaneously hypertensive rats to exogenous angiotensin I and II were determined. Results Synergistic antihypertensive effects were observed when valsartan and benazeprilat were coadministered at subma ximal monotherapy doses in the range 0.5-1.5 mg/kg per day. For all co mbination groups, the area over the curve (mmHg x days) for lowering o f blood pressure was significantly greater (synergy) than that predict ed from the sum of the monotherapy responses. Combination therapy abro gated presser responses to angiotensin I more effectively than did com parable doses of the monotherapies. Conclusions These results demonstr ate that combination therapy aimed at interrupting operation of the re nin-angiotensin system simultaneously at multiple sites can prevent th e partial escape which occurs during chronic angiotensin converting en zyme inhibitor monotherapy, Furthermore, multiple-site intervention re sults in a more efficacious antihypertensive response than that achiev ed with high doses of the individual monotherapies, (C) 1998 Lippincot t-Raven Publishers.