Vasopressin treatment causes widespread hypoxia in the renal medulla of Brattleboro rats

Abstract

In the present study we aimed to elucidate the effects of chronic vasopressin (AVP) administration on renal medullary oxygen levels in AVP-deficient Brattleboro rats (DI rats). To this end, adult DI rats were treated for 3 days with the V2 AVP receptor agonist desmopressin (dDAVP, 5ng/h; 3d) or its vehicle via osmotic minipump. Pimonidazole immunostaining was employed to study oxygen distribution throughout the kidney. In addition, outer medullary gene expression was determined by microarray analysis. dDAVP treatment resulted in a significant drop in urine output (−94 +/− 24% compared to controls, p < .05). Pimonidazole staining was detected in medullary rays of the cortex and in the outer as well as in the inner medulla of dDAVP-treated rats whereas signal in control animals was weak or absent. Gene expression analysis revealed an upregulation of several known target genes for hypoxia-inducible factors which included hexokinase 2, phosphofructokinase, heme oxygenase 1, insulin like growth factor (IGF) 1 and IGF binding proteins 1 and 3. Our results suggest that an activation of the renal urine concentration mechanism by dDAVP causes renal medullary hypoxia and an upregulation of hypoxia-inducible target gene expression. This study was supported by the German Research Foundation (FOR 667)