Beneficial effects of the combination of amlodipine and losartan for lowering blood pressure in spontaneously hypertensive rats

• Published in: Archives of pharmacal research 2009, 32(3), , pp.353-358
• Main Authors: Choi, Seul Min, Seo, Mi Jeong, Kang, Kyung Koo, Kim, Jeong Hoon, Ahn, Byoung Ok, Yoo, Moohi
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Administration, Oral; Amlodipine - administration & dosage; Amlodipine - pharmacology; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Aorta - drug effects; Aorta - physiopathology; Blood Pressure - drug effects; Body Weight - drug effects; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - pharmacology; Cardiomegaly - etiology; Cardiomegaly - prevention & control; Collagen - metabolism; Disease Models, Animal; Drug Therapy, Combination; Hypertension - complications; Hypertension - drug therapy; Hypertension - physiopathology; Losartan - administration & dosage; Losartan - pharmacology; Medicine; Myocardium - metabolism; Pharmacology/Toxicology; Pharmacy; Rats; Rats, Inbred SHR; Time Factors; Vasodilation - drug effects; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-009-1307-x

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.