Objectives Administration of ACE inhibitor (ACEI) and AT1 receptor antagonist (AT1RA) influences ACE2 expression in the heart in myocardial infarcted rats. However, it is unclear how the expression of cardiac ACE2 and ACE changes in hydronephrotic animals treated by ACEI and AT1RA. The present study was to determine if enalapril and losartan affect the expression of cardiac ACE2 and ACE in hydronephrotic mice.
Methods Balb/C mice were anaesthetised with sodium pentobarbitone and the left ureter was ligated except sham-operated animals. Four weeks later, the mice were divided into four groups: the Sham-operated (SO); the left hydronephrotic (LH) alone; LH with enalapril at a dose of 20 mg kg-1d-1 (LH + E) and LH with losartan at a dose of 30 mg kg-1d-1 (LH + L). Two weeks later, plasma renin concentration (PRC), cardiac ACE and ACE2 mRNAs were measured.
Results PRC was greater in LH mice than in the control (P < 0.05). ACE immunostaining in the heart was positive (++) but not ACE2. In LH + E mice, there was a significant increase in ACE2 level in the heart (+++) while ACE expression was not detected. PRC was higher in these mice than that in LH mice (P < 0.01). In LH + L mice, ACE2 immunostaining in the heart was greater than that in the control, but ACE level was reduced.
Conclusions These results indicate that the consequence of hydronephrosis is an increase in the cardiac ACE level while ACE2 is down-graded. There are similar effects of enalapril and losartan in reduced cardiac ACE and the upgraded ACE2 in the hydronephrotic animal model. Thus, not only does hydronephrosis affect the renin activity, but the expression of the cardiac ACE and ACE2 alters. The efficacy of ACEI and AT1RA may be consistent with renin activation by affecting the cardiac RAS.
Acknowledgement This study was supported by the National Natural Science Foundation of China (81270336).