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Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. This implicates reciprocal interactions between the heart and kidney for cardiovascular regulation mediated by the RAS. 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.
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. A whole heart was cut longitudinally and snap-frozen in isopentane/dry ice for immunohistochemical studies after treatment of losartan or enalapril. The expression levels of cardiac ACE, ACE2 and Mas receptor were measured by RT-PCR and Western blot.
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. Plasma Ang II decreased in hydronephrotic mice, but Ang I and II significantly increased after treatment of losartan or enalapril.
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.
This work was supported by Science and Technology Department of Shandong Province (No.2016GSF201207) and the National Natural Science Foundation of China (No. 81270336).