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

Arch Pharm Res. 2009 Mar;32(3):353-8. doi: 10.1007/s12272-009-1307-x. Epub 2009 Apr 23.

Abstract

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.

MeSH terms

  • 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*
  • Myocardium / metabolism
  • Rats
  • Rats, Inbred SHR
  • Time Factors
  • Vasodilation / drug effects
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Vasodilator Agents
  • Amlodipine
  • Collagen
  • Losartan
  • Acetylcholine