Downregulation of Aquaporin-2 Parallels Changes in Renal Water Excretion in Unilateral Ureteral Obstruction
|Title:||Downregulation of Aquaporin-2 Parallels Changes in Renal Water Excretion in Unilateral Ureteral Obstruction|
|Authors:||Frokiaer, Jorgen; Christensen, Birgitte Monster; Marples, David; Djurhuus, Jens; Jensen, Uffe B.; Knepper, Mark; Nielsen, Soren|
|Publisher:||American Journal of Physiology|
|Date Published:||August 01, 1997|
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
It is becoming increasingly established that water reabsorption through the collecting duct is regulated by short- and long-term mechanisms involving VP and AQP2. In the short-term, VP signals AQP2 to insert itself into the cell membrane to make it more water permeable. In the long-term, the number of AQP2s generally available is significantly dependent on the level of VP circulating in the blood.
Other variables such as lithium treatment, low blood potassium, and water retention are associated with changes in the number of AQP2s. These variables can affect the long-term regulation of AQP2, causing a decrease in their numbers which can lead to water balance disorders such as acquired nephrogenic diabetes insipidus (NDI). Obstruction of the ureter (the single fibromuscular tube running from each kidney to the bladder which conveys urine from the kidney to the bladder) also causes down regulation of AQP2s leading to NDI.
In this report, Frokiaer, et al., report on their experiment to determine if the blockage of one of the two ureters, or unilateral ureteral obstruction (UUO), results in any changes in the number and distribution of AQP2s in the kidney collecting duct. If so, the authors wanted to know if the changes were correlated with changes in the volume of urine voided.
In previous research, the authors had shown that obstructing both ureters (bilateral ureteral obstruction - BUO) caused a significant reduction in the number and distribution of AQP2s. The reduction, caused by both systemic changes and changes in the kidney, persisted for seven days after the obstruction was released. It was accompanied by the chronic passage of large volumes of dilute urine. The authors wanted to know if the changes in AQP2 number and distribution (if any) induced by UUO would be caused by systemic changes, local changes in the kidney, or a combination of both.
The authors experimented on rats, binding one of each rat's ureters for a 24-hour period. One group didn't have their obstruction released; another group had theirs released after 24 hours; another group had theirs released after 24 hours and had their urine collected for a two-hour period after the release of the obstruction. There was a control group of rats as well. All the groups had their urine collected during the 24-hour obstruction period. And all had their kidney tissues analyzed.
Frokiaer, et al., found that UUO markedly reduced the number of AQP2s found in the collecting duct cells of the obstructed kidney, and the fewer AQP2s were distributed in the apical membrane of the collecting duct cells. The reduction in number remained 24 hours after the obstruction was released. UUO did not change the rats' total urine output or water intake. The authors speculated that the nonobstructed kidney compensated for the obstructed kidney by doubling its urine output.
Examining the unobstructed kidney revealed that there was a less marked but significant reduction in the number of AQP2s. The AQP2s that were expressed were located more within the cell than in the cell membrane, indicating that the AQP2s were not acting to make the cell membranes more water permeable. That these two factors impaired the collecting duct water reabsorption in the unobstructed kidney was evidenced by the increase in the net amount of solute-free water moving from the blood to the urine. (The level of free-water clearance in the obstructed kidney was even greater.) The reduction in AQP2 numbers was accompanied by less efficient water reabsorption and the inability to concentrate urine. So, the urine voided from the nonobstructed kidney was dilute.
The authors determined that factors within the kidney largely accounted for the downregulation of AQP2s in UUO, though systemic factors could have played a supporting role, as indicated by the reduced AQP2 in the nonobstructed kidney and the continuing downregulation of AQP2 24 hours after obstruction release. Local factors could involve changes in prostaglandin E2 production, changes in intracellular calcium and other changes in the phosphoinositide pathway. In addition, the rate at which AQP2s are synthesized and degraded, both local factors, could be affected by UUO.