Key result
Unilateral ureteral obstruction in rats increased mRNA expressions of ACE1, ET-1, TGF-beta1, ANP, BNP, and CNP, while decreasing ACE2 and NPR-A compared with controls.
Why the study?
Does unilateral ureteral obstruction alter the regulation of RAAS, ET, and NPS in rat kidneys?
Does unilateral ureteral obstruction alter the regulation of RAAS, ET, and NPS in rat kidneys?
In a rat model of unilateral ureteral obstruction, local RAAS and ET-1 are upregulated, potentially driving progressive renal fibrosis, while enhanced NPS activity may serve as a compensatory mechanism.
Answers are grounded in this paper and cite their sources.
Rat model implicates RAAS/ET upregulation and NPS compensation in obstruction; hypothesis-generating for human fibrosis mechanisms.
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.
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Bae et al. (2007) studied Unilateral ureteral obstruction. Unilateral ureteral obstruction vs. Sham treatment (no ligature) was evaluated on mRNA expressions of local renin-angiotensin system, aldosterone synthase, ET-1 and NPS in the cortex. Unilateral ureteral obstruction in rats increased mRNA expressions of ACE1, ET-1, TGF-beta1, ANP, BNP, and CNP, while decreasing ACE2 and NPR-A compared with controls.
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