Long-Term Regulation of Urinary Concentrating Capacity
| Title: | Long-Term Regulation of Urinary Concentrating Capacity |
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| Author: | Knepper, Mark |
| Publisher: | American Journal of Physiology |
| Date Published: | September 01, 1998 |
| Reference Number: | 382 |
Urinary concentrating capacity is regulated in part by a long-term adaptational process involving changes in the absolute abundance of the aquaporin-2 water channel in collecting duct cells. Alterations in aquaporin-2 abundance play key roles in the pathophysiology of several water balance disorders. Escape from the antidiuretic action of vasopressin, e.g. in the syndrome of inappropriate antidiuretic hormone secretion, involves a selective downregulation of aquaporin-2 expression. Excessive water retention causing hyponatremia in volume-expanded states such as congestive heart failure appears to be due in part to a failure of this escape mechanism.
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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)
This form of VP-regulation of AQP2 is called "short-term regulation" and involves the shuttling of AQP2 from within the cell to the cell membrane. VP also regulates in a "long-term fashion by increasing the number of AQP2s in the CD cell. This occurs when there is a sustained elevation of circulating VP levels for 24 hours or more. Researchers presume that the overall ability of the CD principal cells to allow the kidneys to reabsorb body water through them is a function of both short- and long-term regulation of AQP2 by VP.
Sometimes a person can experience a water balance disorder. The kidneys may not be able to reabsorb enough water through the CD, or they may reabsorb too much. In acquired nephrogenic diabetes insipidus (NDI), the patient is unable to reabsorb the required amount of water through the CD. Research indicates that the water transport defect in this disorder is largely the result of the breakdown of the long-term regulation of AQP2 by VP. That is, AQP2s are transported to the cell membrane, but there are much less of them to transport. The water retention resulting from reabsorbing too much water from the CD that leads to congestive heart failure is connected to the hyper-activation of both the short- and long-term regulatory process of VP over AQP2. There is a super abundance of AQP2s and they are being shuttled to the cell membrane.
Sustained elevation of VP increases the numbers of AQP2, which increases the amount of water reabsorbed from the CD. When this occurs and the person it occurs in continues his or her normal water intake, it is possible for that person to retain so much water that he or she develops a deficiency of sodium in the blood called hyponatremia. However, there is a phenomena called "vasopressin escape" which limits the degree of hyponatremia. In vasopressin escape, the body is able to progressively decrease the amount of water the kidneys reabsorb through the CD despite continuing high levels of circulating VP. Somehow the body is able to reduce the number of AQP2s in the CD. Researchers are investigating the vasopressin-escape mechanism and once they understand it, it may be possible to apply the knowledge gained to water balance disorders involving both excessive and inadequate reabsorption of water by the kidney through the CD.