Response of the renal inner medulla to hypoxia: possible defense mechanisms.

Background/aims: Owing to the precarious blood supply to the renal medulla and the high metabolic requirement of the medullary thick ascending limb of Henle's loop, this nephron segment should be especially vulnerable when its supply of O(2) declines.

Methods: Rats were exposed to 8 or 21% O(2) at different time points up to 5 h, and samples were collected for urine flow rate, urine (U(osm)) and renal papillary (RP(osm)) osmolality, urinary excretion of Na(+), Cl(-), K(+) and Mg(2+), blood gases, erythropoietin and vasopressinase activity in plasma. Other groups of rats were pretreated with desmopressin acetate (dDAVP) or underwent bilateral nephrectomy (BNX) 1 h prior to the exposure.

Results: Hypoxic rats had water diuresis (WD) within 2.5 h, as evidenced by lower U(osm) (333 ± 42 mosm/l) and RP(osm) (869 ± 57 mosm/l), thus suggesting that hypoxia led to a failure to achieve osmotic equilibrium within the renal papilla. Circulating vasopressinase activity increased, which was partially renal in origin because it was lower after BNX. The renal concentrating ability during hypoxia was maintained with dDAVP pretreatment, suggesting that dDAVP may have improved O(2) delivery and the active reabsorption of Na(+) in the renal medullary region.

Conclusions: WD or high vasopressinase activity may be valuable diagnostic tools to assess renal medullary hypoxia. Pretreatment with dDAVP may prevent these changes during hypoxia.