Partial ureteral obstruction dysregulates the renal renin-angiotensin system in the fetal sheep kidney.
Publication/Presentation Date
8-1-2001
Abstract
OBJECTIVES: To investigate whether partial ureteral obstruction (PUO) in the fetus induces dysregulation of the renin-angiotensin system (RAS) and of transforming growth factor-beta 1 (TGF-beta1) and tissue inhibitors of metalloproteinase (TIMP1) expression. Previous studies have indicated that renal and urinary tract development depend on an intact renal RAS. Fetal urinary obstruction is distinct from postnatal obstruction. It has been suggested in postnatal animal studies that dysregulation of the RAS, and subsequent increased expression of TGF-beta1 and TIMP1, leads to changes in extracellular matrix composition.
METHODS: Bilateral PUO was created in 4 fetal sheep. Seven animals (four obstructed and three controls) were killed at birth and their kidneys removed. Semiquantitative reverse transcriptase-polymerase chain reaction was used to quantify the levels of renin, angiotensinogen, angiotensin receptor type 1 (AT1 receptor), angiotensin receptor type 2 (AT2 receptor), TGF-beta1, and TIMP1. These messages were normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA.
RESULTS: All obstructed animals had moderate to severe hydronephrosis with enlarged kidneys (mean weight 22.0 g versus 9.4 g for the control animals; P
CONCLUSIONS: Our findings suggest that fetal PUO can cause upregulation of the renal RAS and increased expression of TGF-beta1 and TIMP1, which may alter the balance between the generation and degradation of the extracellular matrix. The coordinate increases in renin, angiotensinogen, and AT1 receptor mRNA levels in chronic fetal PUO may represent a maladaptive response that contributes to interstitial fibrosis and prolonged vasoconstriction. RAS components and growth factors, particularly TGF-beta1, may be considered relevant targets in the prevention and treatment of congenital obstructive nephropathy.
Volume
58
Issue
2
First Page
301
Last Page
306
ISSN
1527-9995
Published In/Presented At
Ayan, S., Roth, J. A., Freeman, M. R., Bride, S. H., & Peters, C. A. (2001). Partial ureteral obstruction dysregulates the renal renin-angiotensin system in the fetal sheep kidney. Urology, 58(2), 301–306. https://doi.org/10.1016/s0090-4295(01)01156-6
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
11489731
Department(s)
Department of Pediatrics
Document Type
Article