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1 Pharmaforschungszentrum, Bayer AG, Wuppertal, Germany
2 Department of Physiology, University of Regensburg, Regensburg, Germany
3 Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark
4 Institute of Pathology, Odense University Hospital, Odense, Denmark
5 Department of Urology, Odense University Hospital, Odense, Denmark
* To whom correspondence should be addressed. E-mail: bljensen{at}health.sdu.dk.
To investigate regional aspects of hypoxic regulation of adrenomedullin (AM) in kidneys, we mapped the distribution of AM in rat kidney after hypoxia (normobaric hypoxic hypoxia, carbon monoxide and CoCl2 for 6h), anemia (hematocrit lowered by bleeding) and after global transient ischemia (unilateral renal artery occlusion 1h-reperfusion for 6 and 24h) and segmental infarct (6h and 24h). AM expression and localization was determined in normal human kidney and in kidneys with arterial stenosis. Hypoxia stimulated AM mRNA expression significantly in rat inner medulla (CO 13-times, 8% O2 6-times and CoCl2 8-times), followed by outer medulla and cortex. AM mRNA level was significantly elevated in response to anemia and occlusion-reperfusion. Immunoreactive AM was associated with thin limbs of Henle's loop, distal convoluted tubule, collecting ducts, papilla surface epithelium and urothelium. AM labeling was prominent in inner medulla after CO and in outer medulla after occlusion-reperfusion. The infarct border zone was strongly labeled for AM. In cultured inner medullary collecting duct cells, AM mRNA was significantly increased by hypoxia. AM mRNA was equally distributed in human kidney and AM was localized as in rat. In human kidneys with artery stenosis, AM mRNA was not significantly enhanced compared to controls, but AM-immunoreactivity was observed in tubules, vessels and glomerular cells. In summary, AM expression was increased in rat kidney in response to hypoxic and ischemic hypoxia in keeping with oxygen gradients. AM was widely distributed in human kidney with arterial stenosis. AM may play a significant role to counteract hypoxia in the kidney.
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