To investigate regional aspects of hypoxic regulation of
adrenomedullin (AM) in kidneys, we mapped the distribution of AM in the rat kidney after
hypoxia (normobaric hypoxic
hypoxia,
carbon monoxide, and
CoCl(2) for 6 h),
anemia (hematocrit lowered by
bleeding) and after global transient
ischemia for 1 h (unilateral renal artery occlusion and reperfusion for 6 and 24 h) and segmental
infarct (6 and 24 h). AM expression and localization was determined in normal human kidneys and in kidneys with arterial
stenosis.
Hypoxia stimulated AM
mRNA expression significantly in rat inner medulla (CO 13 times, 8% O(2) 6 times, and
CoCl(2) 8 times), followed by the outer medulla and cortex. AM
mRNA level was significantly elevated in response to
anemia and occlusion-reperfusion. Immunoreactive AM was associated with the thin limbs of Henle's loop, distal convoluted tubule, collecting ducts, papilla surface epithelium, and urothelium. AM labeling was prominent in the inner medulla after CO and in the 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 the rat kidney. In human kidneys with artery
stenosis, AM
mRNA was not significantly enhanced compared with controls, but AM immunoreactivity was observed in tubules, vessels, and glomerular cells. In summary, AM expression was increased in the rat kidney in response to hypoxic and ischemic
hypoxia in keeping with
oxygen gradients. AM was widely distributed in the human kidney with arterial
stenosis. AM may play a significant role to counteract
hypoxia in the kidney.