Chronic activation of vasopressin V2 receptor signalling lowers renal medullary oxygen levels in rats

作者：Dietrich A; Mathia S; Kaminski H; Mutig K; Rosenberger C; Mrowka R; Bachmann S; Paliege A^*

来源：Acta Physiologica, 2013, 207(4): 721-731.

DOI：10.1111/apha.12067

• gene expression analysis
• gene ontology analysis
• hypoxia-inducible factor
• pimonidazole
• urine concentrating

Aim In the present study, we aimed to elucidate the effects of chronic vasopressin administration on renal medullary oxygen levels. Methods Adult Sprague Dawley or vasopressin-deficient Brattleboro rats were treated with the vasopressin V2 receptor agonist, desmopressin (5ng/h; 3d), or its vehicle via osmotic minipumps. Immunostaining for pimonidazole and the transcription factor HIF-1 (hypoxia-inducible factor-1) were used to identify hypoxic areas. Activation of HIF-target gene expression following desmopressin treatment was studied by microarray analysis. Results Pimonidazole staining was detected in the outer and inner medulla of desmopressin-treated rats, whereas staining in control animals was weak or absent. HIF-1 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*1021). Regulated products included insulin-like growth factor binding proteins 1 and 3, angiopoietin 2, fibronectin, cathepsin D, hexokinase 2 and cyclooxygenase 2. Conclusion 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.

• 出版日期2013-4