pituitrin and pimonidazole

In the present study, we aimed to elucidate the effects of chronic vasopressin administration on renal medullary oxygen levels.. Adult Sprague Dawley or vasopressin-deficient Brattleboro rats were treated with the vasopressin V2 receptor agonist, desmopressin (5 ng/h; 3d), or its vehicle via osmotic minipumps. Immunostaining for pimonidazole and the transcription factor HIF-1α (hypoxia-inducible factor-1α) were used to identify hypoxic areas. Activation of HIF-target gene expression following desmopressin treatment was studied by microarray analysis.. Pimonidazole staining was detected in the outer and inner medulla of desmopressin-treated rats, whereas staining in control animals was weak or absent. HIF-1α immunostaining demonstrated nuclear accumulation in the papilla of desmopressin-treated animals, whereas no staining was observed in the controls. Gene expression analysis revealed significant enrichment of HIF-target genes in the group of desmopressin-regulated gene products (P = 2.6*10(-21) ). Regulated products included insulin-like growth factor binding proteins 1 and 3, angiopoietin 2, fibronectin, cathepsin D, hexokinase 2 and cyclooxygenase 2.. Our results demonstrate that an activation of the renal urine concentrating mechanism by desmopressin causes renal medullary hypoxia and an upregulation of hypoxia-inducible gene expression.

Topics: Animals; Deamino Arginine Vasopressin; Disease Models, Animal; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney Medulla; Nitroimidazoles; Oxygen; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Receptors, Vasopressin; Signal Transduction; Vasopressins