Beneficial effects of the combination of amlodipine and losartan for lowering blood pressure in spontaneously hypertensive rats.
A combination of antihypertensive agents can better control blood pressure and reduce the number and severity of side effects than a monotherapy. Since both CCBs (calcium channel blockers) and ARBs (angiotensin II receptor type-1 blockers) are current and effective antihypertensive drugs, this study assessed the synergistic antihypertensive effects as well as the optimal combination ratio of these two drugs. Amlodipine (3 mg/kg) or losartan (30 mg/kg) alone or a combination of each drug at a ratio 1:10 and 1:20 was administered orally to spontaneously hypertensive rats (SHR). A four-week treatment of either 3 mg/kg amlodipine or 30 mg/kg losartan alone decreased the systolic blood pressure (SBP). However, their combination significantly lowered the SBP from the 3(rd) week, and there was a positive correlation between this reduction in blood pressure and the improvement in arterial endothelium-dependent relaxation. In addition, the combination therapy (1:20) decreased both the cardiac mass and left ventricular weight to a greater extent than with either amlodipine or losartan alone. The collagen content in the cardiac tissue was also significantly lower after the 4-week combination therapy (1:10). These results suggest that the combined use of amlodipine and losartan might be more effective in treating hypertension than a monotherapy.
Choi
Seul Min
SM
Research Center, Dong-A Pharmaceutical Company, Yongin, 446-905, Korea. csm@donga.co.kr
Seo
Mi Jeong
MJ
Kang
Kyung Koo
KK
Kim
Jeong Hoon
JH
Ahn
Byoung Ok
BO
Yoo
Moohi
M
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D017311:Amlodipine; D003094:Collagen; D019808:Losartan; D000109:Acetylcholine