RGD Reference Report - Increased renal adrenomedullin expression in rats with ureteral obstruction. - Rat Genome Database

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Increased renal adrenomedullin expression in rats with ureteral obstruction.

Authors: Norregaard, R  Bodker, T  Jensen, BL  Stodkilde, L  Nielsen, S  Frokiaer, J 
Citation: Norregaard R, etal., Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R185-92. Epub 2008 Oct 22.
RGD ID: 2325637
Pubmed: PMID:18945953   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpregu.00170.2008   (Journal Full-text)

Ureteral obstruction is characterized by decreased renal blood flow that is associated with hypoxia within the kidney. Adrenomedullin (AM) is a peptide hormone with tissue-protective capacity that is stimulated through hypoxia. We tested the hypothesis that ureteral obstruction stimulates expression of AM and hypoxia-inducible factor-1 (HIF-1alpha) in kidneys. Rats were exposed to bilateral ureteral obstruction (BUO) for 2, 6, 12, and 24 h or sham operation and compared with unilateral obstruction (UUO). AM mRNA expression was measured by quantitative PCR in cortex and outer medulla (C+OM) and inner medulla (IM). AM and HIF-1alpha protein abundance and localization were determined in rats subjected to 24-h BUO. AM mRNA expression in C+OM increased significantly after 12-h BUO and further increased after 24 h. In IM, AM mRNA expression increased significantly in response to BUO for 6 h and further increased after 24 h. AM peptide abundance was enhanced in C+OM and IM after 24-h BUO. Immunohistochemical labeling of kidneys showed a wider distribution and more intense AM signal in 24-h BUO compared with Sham. In UUO rats, AM mRNA expression increased significantly in IM of the obstructed kidney compared with nonobstructed and Sham kidney whereas AM peptide increased in IM compared with Sham. HIF-1alpha protein abundance increased significantly in IM after 24-h BUO compared with Sham and HIF-1alpha immunoreactive protein colocalized with AM. In summary, AM and HIF-1alpha expression increases in response to ureteral obstruction in agreement with expected oxygen gradients. Hypoxia acting through HIF-1alpha accumulation may be an important pathway for the renal response to ureteral obstruction.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ureteral obstruction  ISOAdm (Rattus norvegicus)2325637; 2325637mRNA and protein:increased expression:kidneyRGD 
ureteral obstruction  IEP 2325637mRNA and protein:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Adm  (adrenomedullin)

Genes (Mus musculus)
Adm  (adrenomedullin)

Genes (Homo sapiens)
ADM  (adrenomedullin)

Additional Information