Chronic Treatment with Angiotensin-converting Enzyme Inhibitor Increases Cardiac Fibrosis in Young Rats Submitted to Early Ovarian Failure

Background: We investigated whether the treatment with enalapril maleate, combined with aerobic physical training, promotes positive effects on the autonomic balance, the morphology and the cardiac function in female rats submitted to early ovarian failure.

Methods: Thirty-five female Wistar rats, ovariectomized at 10weeks of age, were assigned into Ovariectomized rats (OVX) and Ovariectomized rats treated with enalapril maleate (OVX-EM, 10mg·kg·d) Each group was subdivided into sedentary and trained (aerobic swimming training for 10weeks). All animals were submitted to a) double pharmacological autonomic blockade, b) study of morphology and cardiac function by echocardiography, and c) analysis of cardiac fibrosis.

Results: The OVX-EM sedentary group showed a significant increase in cardiac fibrosis, relative heart weight, interventricular septum thickness and increased sympathetic participation and reduced participation of the vagal tone in the determination of the basal heart rate when compared to the OVX sedentary group. Physical training reduced cardiac fibrosis in both groups, however, with less intensity in the OVX-EM group. It also increased the absolute and relative heart weight and the end-systolic volume. Finally, the OVX-EM trained group showed higher values for left ventricular end-systolic volume and lower values for ejection fraction and shortening fraction than the sedentary OVX-EM group.

Conclusion: Enalapril maleate exacerbated cardiac fibrosis and increased sympathetic participation in the basal heart rate determination, without significantly affecting the cardiac function. Aerobic physical training did not change the cardiac autonomic control, but reduced cardiac fibrosis and had little effect on the cardiac function.