Hydronephrosis decreases ACE2 and mas receptor expression in the heart


Authors: Wu Junyan1, Wang Lei2, Zhou Jiansheng3, Zhang Yanling1

1Institute of Cardiovascular Diseases, Taian Maternal and Children’s Hospital, Taian, China

2Department of Pediatric Surgery, Soochow University Affiliated Children’s Hospital, Suzhou, China

3John Curtin School of Medical Research, Australian National University, Australia

OBJECTIVES Hydronephrosis is commonly caused by an obstruction of the urine flow from the kidney. The condition involves a dilation and distention of the renal pelvis. Hydronephrosis may be either acute or chronic in nature. It was reported a postnatal infant had hypoplastic left heart with hydronephrosis, indicating that there may be a relationship between hydronephrosis and heart disease. However, whether hydronephrosis causes cardiac damage and affects the RAS in the heart remains unknown. Thus, we assessed BP, heart weight and the expression of components of the RAS in the heart 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. At postmortem, heart weight was balanced. 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 In the normal kidney the tubules were intact while they disappeared in the hydronephrotic kidney. Blood pressure did not significantly change after the left ureteral ligation. 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.

CONCLUSIONS In this study, we found that Hydronephrosis increased cardiac ACE, suppressed ACE2 and Mas receptor levels. Furthermore, 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. These findings may lead to an exciting new area in the clinical administration of AT1 receptor blockade. These results also suggest that activation of cardiac ACE2 by both enalapril and losartan may protect against the adverse effects of activated RAS and renal impairment. Thus, we propose that the change of cardiac ACE2 and Mas receptor expression induced by hydronephrosis can be an important target of strategies for preventing cardiovascular damage. The observations of the different molecular mechanisms of losartan and enalapril could be helpful for better options in the treatment of cardiovascular diseases.

This study was supported by Science and Technology Department of Shandong Province (No. 2016GSF201207) and the Natural Science Foundation of China (No. 81270336). *equal contribution; #Correspondence.

Updated: November 19, 2019 — 2:52 pm