Vasopressin-independent regulation of collecting duct aquaporin-2 in food deprivation

Abstract

Humans and animals are frequently subjected to food deprivation or starvation. However, the adaptation of the kidney to this condition is not well understood. The purpose of these studies was to examine the effects of food deprivation on water handling by the kidney, the expression levels of collecting duct (CD) water channel aquaporin-2 (AQP2), and to determine the role of vasopressin in the adaptation of AQP2 to food deprivation. Sprague-Dawley (SD) and Brattleboro rats were placed in metabolic cages and deprived of food but had free access to water for 72 hours. Water balance and urine osmolality were measured daily. Kidney tissues were isolated and examined for the expression of AQP2 using semiquantitative immunoblotting and Northern hybridization. The circulating level of vasopressin and the mRNA expression levels of its precursor were determined by radioimmunoassay and Northern hybridization, respectively. In SD rats, the first 24 hours of food deprivation is associated with a significant polyuria and decreased urine osmolality (Uosm). This correlated with a significant down-regulation of AQP2 in the cortex and outer medulla. After 72 hours of food deprivation, Uosm increased above baseline, and urine volume dropped to a lower value. This was associated with a rebound increase in AQP2 expression in the cortex and OM and its up-regulation in the inner medulla. Interestingly, vasopressin mRNA expression and plasma levels were unchanged during food deprivation. Further, in homozygous Brattleboro rats, in which endogenous vasopressin is absent, food deprivation caused changes in urine volume, urine osmolality, and AQP2 expression, which are qualitatively similar to those observed in normal rats. Food deprivation impairs water handling by the kidney by causing dual changes in urine volume and urine osmolality. This effect is associated with parallel alterations in the expression of AQP2 and is independent of vasopressin activity. It is concluded that the increase in water reabsorption in the CD is an adaptive response of the kidney to a long period of food deprivation and is mediated via a vasopressin-independent mechanism.