Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla

Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla.BackgroundEndotoxemia can lead to fluid metabolism alterations despite unchanged or elevated plasma vasopressin (VP) levels, suggesting a refractoriness of the kidney to the effect of the peptide. To test this hypothesis, we examined the effect of lipopolysaccharide (LPS) injection on the expression of V2 receptors and aquaporin-2 in the kidney.MethodsPlasma VP and urine osmolality, and binding of [3H]VP to kidney membranes, Western blot, and immunohistochemical analysis of aquaporin-2, in situ hybridization for V2 VP receptors and cytokines mRNAs were measured in the kidney 3 to 24hours after LPS injection, 250 μg/100 g, intraperitoneally.ResultsLPS injection caused prolonged decreases in urine osmolality (up to 24hours) without significant changes in plasma levels of sodium or VP. This was associated with marked decreases in V2 VP receptor mRNA and VP receptor number in the kidney, which were evident for up to 12hours after LPS injection. Aquaporin-2 in kidney inner medulla was also reduced by about 50%. LPS induced interleukin (IL)-1β in the kidney medulla by 3hours, reached maximum at 6hours, and started to decline by 12hours, while it increased IL-6 mRNA significantly only at 3hours. Interleukin mRNA expression was absent in kidneys of control rats. In vitro incubation of kidney medulla slices with IL-1β reduced VP binding.ConclusionThe inflammatory response to acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney inner medulla resulting in prolonged impairment of the renal capacity to concentrate urine