Cilnidipine, An L-/N-Type Calcium Channel Blocker, Changes the Circulating Angiotensin?(1-7)/Angiotensin II RatioShizuka Aritomi1*, Kazumi Niinuma1, Mai Kawakami1, Tarou Nakamura1, Tomoyuki Konda1, Makoto Shiozaki1 and Michihiro Yoshimura2
- *Corresponding Author:
- Dr. Shizuka Aritomi
E-mail: [email protected]
Received December 22, 2011; Accepted Date: January 22, 2012; Published Date: January 26, 2012
Citation: Aritomi S, Niinuma K, Kawakami M, Nakamura T, Konda T, et al. (2012) Cilnidipine, An L-/N-Type Calcium Channel Blocker, Changes the Circulating Angiotensin–(1-7)/Angiotensin II Ratio. J Hypertens Open Access 1:102. doi: 10.4172/2167-1095.1000102
Copyright: © 2012 Aritomi S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
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.