Cardioprotective effects of low-dose combination therapy with a statin and an angiotensin receptor blocker in a rat myocardial infarction model

摘要

Purpose: Statins attenuate angiotensin II-induced myocyte hypertrophy and this might increase the cardioprotective effects of renin-angiotensin system inhibition in the ischemic heart. In this study, we investigated the cardioprotective effects of combination therapy with low-dose simvastatin and low-dose losartan using a rat myocardial infarction model. Methods: Myocardial infarction was created in rats by left anterior descending artery ligation, and the animals were randomly allocated to one of four groups: control (n= 8), losartan 3. mg/kg/day (n= 8), simvastatin 2. mg/kg/day (n= 8), and losartan 3. mg/kg/day plus simvastatin 2. mg/kg/day (n= 8). Each treatment was started on the day of coronary ligation, and hemodynamics, myocardial blood flow, and infarct size were measured after 28 days. Results: Blood pressure, heart rate, and left ventricular systolic and end-diastolic pressures were not significantly different comparing the control group with the 3 other treatment groups. The peak positive first derivative of left ventricular pressure (peak LV dP/. dt) was equivalent comparing the control group with the losartan and simvastatin groups. However, the peak LV dP/. dt was greater in the losartan plus simvastatin group than in the control group (p<. 0.05). Myocardial blood flow, left ventricular weight, and infarct size were not significantly altered by the 3 treatments. Conclusions: Treatment with 3. mg/kg/day losartan plus 2. mg/kg/day simvastatin but not losartan or simvastatin alone improved left ventricular systolic function in a rat myocardial infarction model. The result suggests that statins given in combination with angiotensin receptor blockers might have beneficial cardioprotective effects, even at low-doses for each agent.