Related Experiment Videos
Perindopril reverses myocyte remodeling in the hypertensive heart
Tatsuyuki Onodera1, Fumiko Okazaki, Hidekazu Miyazaki
1Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. tonodera@jikei.ac.jp
Insights
Angiotensin converting enzyme (ACE) inhibitors reversed cardiac hypertrophy in hypertensive rats by reducing myocyte volume. Beta blockade did not affect myocyte remodeling, suggesting the renin-angiotensin system is key in hypertension-induced cardiac changes.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Hypertension Research
Background:
- The renin-angiotensin system (RAS) is implicated in hypertension-related cardiac remodeling.
- The specific role of RAS in myocyte remodeling remains incompletely understood.
Purpose of the Study:
- To evaluate the role of RAS in myocyte remodeling using perindopril, an ACE inhibitor, in spontaneously hypertensive rats (SHRs).
- To investigate the impact of beta-blockade on myocyte remodeling in the same model.
Main Methods:
- Female SHRs were divided into four groups: control, low-dose perindopril, high-dose perindopril, and bisoprolol (beta-blocker).
- Left ventricular (LV) myocytes were isolated after 4 weeks of treatment for morphological analysis.
- Measurements included LV myocyte volume, cross-sectional area, and length.
Main Results:
- Perindopril treatment (both low and high doses) significantly reduced LV myocyte volume and cross-sectional area compared to controls.
- High-dose perindopril also decreased LV myocyte length.
- Bisoprolol treatment showed no significant morphological changes in LV myocytes compared to the control group.
Conclusions:
- ACE inhibitors effectively reversed cardiac hypertrophy in SHRs, primarily by reducing LV myocyte volume.
- Beta-blockade did not reverse myocyte remodeling in this model.
- These findings highlight the critical role of the RAS in mediating myocyte remodeling within the hypertensive heart.
Abstract:
Studies have shown that the renin-angiotensin system (RAS) plays an important role in cardiac remodeling induced by hypertension. However, the role of this system on myocyte remodeling remains unclear. In the present study, we have assessed the effect of perindopril, an angiotensin converting enzyme (ACE) inhibitor, in spontaneously hypertensive rats (SHRs) as a means to evaluate the role of RAS in myocyte remodeling. We also investigated the effect of beta blockade on myocyte remodeling. We used female SHRs at 12 weeks of age. They were divided into four experimental groups: a control group, group C; low dose perindopril group (0.3 mg/kg/day, p.o.), group PL; high dose perindopril group (3 mg/kg/day, p.o.), group PH; and bisoprolol group (60 mg/kg/day, p.o.), group B. We isolated myocytes from these rats after 4 weeks. LV myocyte volume and cross-sectional area decreased in groups PL and PH compared to group C. LV myocyte length decreased in group PH compared to group C. However, there was no morphological change in LV myocytes in group B compared to group C. In summary, ACE inhibitors reversed cardiac hypertrophy mainly by a reduction in LV myocyte volume; however, beta blockade did not reverse myocyte remodeling. These results suggest that RAS plays an important role in myocyte remodeling in the hypertensive heart.