What is the clinical evidence from this study?

Study design: Other. Population: Hypertension (Spontaneously hypertensive rats) (n=31). Intervention: Perindopril vs. Control (water) or Bisoprolol. Primary outcome: Left ventricular myocyte volume (47% reduction (high dose), p=<0.05).

January 1, 2002Open Access

Perindopril Reverses Myocyte Remodeling in the Hypertensive Heart

Q: What are the key findings of this study?

Perindopril reversed cardiac hypertrophy by reducing left ventricular myocyte volume by up to 47% in spontaneously hypertensive rats, whereas bisoprolol did not reverse myocyte remodeling.

Key Result

Perindopril reversed cardiac hypertrophy by reducing left ventricular myocyte volume by up to 47% in spontaneously hypertensive rats, whereas bisoprolol did not reverse myocyte remodeling.

Structured PICO

Does perindopril or bisoprolol reverse myocyte remodeling in spontaneously hypertensive rats?

Population

31 female spontaneously hypertensive rats at 12 weeks of age were treated for 4 weeks to evaluate the effect of perindopril and bisoprolol on myocyte remodeling.

Intervention

Perindopril (low dose 0.3 mg/kg/day or high dose 3 mg/kg/day, oral) or bisoprolol (60 mg/kg/day, oral) administered in drinking water for 4 weeks.

Comparator

Control group receiving no active drug.

Outcome

Left ventricular myocyte volume, cross-sectional area, and cell length measured from isolated myocytes after 4 weeks.surrogate

ACE inhibition with perindopril, but not beta-blockade with bisoprolol, reverses myocyte remodeling in hypertensive rats independently of reductions in left ventricular wall stress.

Main Result

Effect estimate: 47% reduction (high dose)

p-value: p=<0.05

Limitations

Did not investigate fibrotic and vascular changes in the heart
Limitations regarding the development of heart failure

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.

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