Choi Seul Min, Seo Mi Jeong, Kang Kyung Koo, Kim Jeong Hoon, Ahn Byoung Ok, Yoo Moohi
Research Center, Dong-A Pharmaceutical Company, Yongin, 446-905, Korea.
Arch Pharm Res. 2009 Mar;32(3):353-8. doi: 10.1007/s12272-009-1307-x. Epub 2009 Apr 23.
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.
与单一疗法相比,联合使用抗高血压药物能更好地控制血压,并减少副作用的数量和严重程度。由于钙通道阻滞剂(CCB)和血管紧张素II 1型受体阻滞剂(ARB)都是目前有效的抗高血压药物,本研究评估了这两种药物的协同降压作用以及最佳联合比例。将氨氯地平(3毫克/千克)或氯沙坦(30毫克/千克)单独给药,或以1:10和1:20的比例联合给药,口服给予自发性高血压大鼠(SHR)。单独给予3毫克/千克氨氯地平或30毫克/千克氯沙坦进行为期四周的治疗可降低收缩压(SBP)。然而,它们的联合使用从第3周起显著降低了SBP,并且血压的这种降低与动脉内皮依赖性舒张功能的改善之间存在正相关。此外,联合治疗(1:20)比单独使用氨氯地平或氯沙坦更能显著降低心脏重量和左心室重量。在为期4周的联合治疗(1:10)后,心脏组织中的胶原蛋白含量也显著降低。这些结果表明,氨氯地平和氯沙坦联合使用治疗高血压可能比单一疗法更有效。