Altered regulation of renin-angiotensin, endothelin and natriuretic peptide systems in rat kidney with chronic unilateral ureteral obstruction.

BACKGROUND

The present study was designed to investigate the role of the local renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and the natriuretic peptide system (NPS) for the development of renal fibrosis and progressive renal disease in experimental unilateral ureteral obstructed (UUO) rats.

METHODS

Male Sprague-Dawley rats (180-200 g) were unilaterally obstructed by ligation of the proximal ureters for 14 days. Control rats were treated in the same way, except that no ligature was made. The mRNA expressions of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET-1 and NPS was determined in the cortex by real-time polymerase chain reaction.

RESULTS

Following the unilateral ureteral obstruction, the mRNA expressions of angiotensin-converting enzyme 1, ET-1 and transforming growth factor-beta1 (TGF-beta1) were increased, while angiotensin-converting enzyme 2 was decreased in the obstructed kidney compared with the controls. Angiotensin II type 1 receptor was decreased and TGF-beta1 was not changed in contralateral kidney compared with the controls. Atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide expressions were increased in UUO kidneys compared with the controls, while natriuretic peptide receptor-A was decreased in UUO kidneys.

CONCLUSION

The local RAAS and ET-1 was upregulated which may play a role in the progressive renal fibrosis in obstructed kidneys in rats with UUO. The enhanced activity of NPS in UUO kidney may play a role to compensate against progressive renal fibrosis in chronic obstructive uropathy.