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Am J Physiol Regul Integr Comp Physiol 296: R185-R192, 2009. First published October 22, 2008; doi:10.1152/ajpregu.00170.2008
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WATER AND ELECTROLYTE HOMEOSTASIS

Increased renal adrenomedullin expression in rats with ureteral obstruction

Rikke Nørregaard,1,2,* Tina Bødker,1,2,* Boye L. Jensen,4 Lene Stødkilde,1,2 Søren Nielsen,1,3 and Jørgen Frøkiær1,2

1The Water and Salt Research Center, 2Institute of Clinical Medicine, and 3Institute of Anatomy, University of Aarhus, Aarhus, Denmark; and 4Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark

Submitted 6 March 2008 ; accepted in final form 20 October 2008

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-1{alpha}) 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-1{alpha} 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-1{alpha} protein abundance increased significantly in IM after 24-h BUO compared with Sham and HIF-1{alpha} immunoreactive protein colocalized with AM. In summary, AM and HIF-1{alpha} expression increases in response to ureteral obstruction in agreement with expected oxygen gradients. Hypoxia acting through HIF-1{alpha} accumulation may be an important pathway for the renal response to ureteral obstruction.

hypoxia-inducible factor-1{alpha}; bilateral ureteral obstruction; medullary hypoxia; inflammation; tumor neurosis factor {alpha}


Address for reprint requests and other correspondence: J. Frøkiær, The Water and Salt Research Center, Clinical Institute, Univ. of Aarhus, Dept. of Clinical Physiology and Nuclear Medicine, Aarhus Univ. Hospital-Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark (e-mail: jf{at}ki.au.dk)






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