Comparison of effects of L/N‐type and L‐type calcium channel blockers on post‐infarct cardiac remodelling in spontaneously hypertensive rats

Abstract

Hypertension and coronary events are becoming more prevalent in aging societies, and myocardial infarction usually occurs in calcium channel blocker (CCB)‐treated hypertensive patients. We herein compared the effects of cilnidipine, an L/N‐type CCB and amlodipine, an L‐type CCB, on post‐infarct left ventricular (LV) remodeling in spontaneously hypertensive rats (SHRs). Male SHRs were subjected to 30 minutes of left coronary artery occlusion followed by reperfusion (MI group). The administration of cilnidipine (10 mg/kg/day; MI+Cil group) or amlodipine (10 mg/kg/day; MI+Aml group) was initiated one week before surgery and continued for five weeks. Both CCBs decreased blood pressure. Four weeks after surgery, cilnidipine, but not amlodipine, attenuated LV dilatation, fractional shortening impairments, end‐diastolic pressure elevations, and tau elongation. In the non‐infarct region, myocyte hypertrophy and brain natriuretic peptide (BNP) mRNA levels were similarly attenuated by both CCBs. On the other hand, interstitial fibrosis, the mRNA expression of collagen type III and TGF β and immunohistological TGF β protein expression in the non‐infarct region were reduced more in the MI+Cil group than in the MI+Aml group. Additionally, elevated angiotensin‐converting enzyme activity and interstitial norepinephrine concentrations in the non‐infarct region were reduced by cilnidipine. These results suggest that cilnidipine reduced cardiac norepinephrine concentrations and inhibited the renin‐angiotensin system, which attenuated post‐infarct remodeling more than amlodipine in hypertensive rats.