Synergistic decrease in blood pressure by captopril combined with losartan in spontaneous hypertensive rats.
This study was designed to examine the anti-hypertensive effect of the combination therapy of captopril with losartan by oral administration using both independent and cross-over experimental protocols. In independent experimental protocols, four different groups of spontaneous hypertensive rats (SHR) were treated for 1 or 2 weeks: control, captopril (20 mg/kg/day), losartan (20 mg/kg/day), and combination captopril (10 mg/kg/day) with losartan (10 mg/kg/day). In cross-over protocols, each SHR received all four treatments for 1 or 3 days with an interval of several days between each injection for washing-out and return to high blood pressure (BP) levels. BP and heart rate (HR) were measured in conscious telemetered SHR. According to the results from the independent protocol, regardless of a 1- or 2-week administration period, combination therapy with low doses of captopril and losartan had a greater anti-hypertensive effect than individual high-dose monotherapy. Similarly, results from the cross-over protocol showed that regardless of 1-day or 3-day administration, the decrease in BP in the 11(th) and 12(th) hour after administration was greatest with the combination of low-dose captopril and losartan. Therefore, combination therapy with low doses of captopril with losartan lowered BP to a greater extent than a high dose of either individual monotherapy.
Shin
Chang-Yong
CY
College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.
Choi
Woon-Seok
WS
Yi
Inseon
I
Nan
Mei-Hua
MH
Myung
Chang-Seon
CS
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D000959:Antihypertensive Agents; D002216:Captopril; D019808:Losartan