உயர் இரத்த அழுத்த இதழ்: திறந்த அணுகல்

Cilnidipine, An L-/N-Type Calcium Channel Blocker, Changes the Circulating Angiotensin?(1-7)/Angiotensin II Ratio

Abstract

Shizuka Aritomi

Objective:It is well known that cilnidipine, which is a L/N-type calcium channel blocker (CCB), has Angiotensin (Ang) II lowering effects that result in organ protective effects compared to L-type CCBs. However, a recent study indicated that angiotensin-converting enzyme (ACE) 2, which is expressed in the heart and kidney, metabolizes Ang II to Ang-(1-7), which is a peptide that has organ-protective effects. In this study, we compared the effects of the L-/N-type CCB cilnidipine and the L-type CCB amlodipine on plasma Ang peptides in a rat hypertensive model.

Methods:Eight-week-old Sprague-Dawley rats were administered a chronic infusion of Ang II through an osmotic mini-pump, along with vehicle, cilnidipine, or amlodipine for 28 days, and the plasma renin-angiotensin-aldosterone system (RAAS) levels were examined.

Results:Cilnidipine and amlodipine exerted equivalent antihypertensive effects. As for Ang peptides, amlodipine induced increases in Ang I levels and decreases in Ang-(1-7)/Ang I ratios. However, the cilnidipine group showed significantly higher Ang-(1-7)/Ang II ratios than the control group. As for gene expression, amlodipine significantly decreased the ratio of ACE2/ACE. Moreover, only cilnidipine treatment resulted in a significant reduction in cardiac fibrosis.

Conclusions:The results of the present study demonstrate that the L-/N-type CCB cilnidipine changed the balance between Ang-(1-7) and Ang II and increased the proportion of Ang-(1-7). Taken together, these results suggest that the suppressing the expansion of the area of cardiac fibrosis of cilnidipine is due to increases in the activity of the ACE2-Ang-(1-7) arm.