Alteration Of Cardiac Ace2 And Mas Receptor Expression In Hydronephrotic Mice

Objectives: Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Methods: Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. Blood pressure was measured by the tail-cuff method using photoelectric volume oscillometry. The levels of cardiac ACE, ACE2 and Mas receptor were measured by RT-PCR and Western blot after treatment of losartan or enalapril. Plasma renin activity (PRA), Ang I and Ang II were measured by radioimmunoassay using commercial kits. Results: Hydronephrosis led to an increase of ACE level and a decreased of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (P < 0.01). Enalapril increased ACE2 levels (P < 0.01), but did not affect Mas receptor in the heart. PRA decreased in hydronephrotic mice, but significantly increased by losartan or enalapril. Plasma Ang II level decreased in hydronephrotic mice (P < 0.05). Administration of losartan was accompanied by a rise in plasma Ang I and Ang II concentrations in hydronephrotic animals (P < 0.05). Enalapril also increased levels of Ang I (P < 0.01) and Ang II (P < 0.05) in the circulation. Conclusion: Hydronephrosis increased cardiac ACE, suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals.