The Experts below are selected from a list of 1335 Experts worldwide ranked by ideXlab platform
Joseph G. Verbalis - One of the best experts on this subject based on the ideXlab platform.
-
an antifungal for Antidiuresis
2019Co-Authors: Joseph G. VerbalisAbstract:The article by Vukicevic et al. [1][1] in this issue of the Journal of the American Society of Nephrology reports effects of fluconazole to increase osmotic water transport in renal collecting ducts by arginine vasopressin (AVP)–independent effects on trafficking of aquaporin-2 (AQP2) water
-
euvolemic hyponatremia secondary to the syndrome of inappropriate Antidiuresis
2019Co-Authors: Joseph G. VerbalisAbstract:Euvolemic hyponatremia is the most common cause of hyponatremia in both hospitalized patients and outpatients. The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate Antidiuresis (SIAD). Diagnosis of SIAD involves evaluation of a set of long-standing clinical and laboratory criteria for this diagnosis. Many treatment options for SIAD exist, and choosing among them should be based on the chronicity of the hyponatremia and neurological symptomatology. Importantly, clinical judgment and risk/benefit analysis that is individualized for specific patients should drive therapeutic decisions, because there is no single treatment that represents the "best" therapy for all patients with SIAD.
-
Sex differences in vasopressin V2 receptor expression and vasopressin-induced Antidiuresis
2010Co-Authors: Jun Liu, Kathryn Sandberg, Nikhil Sharma, Wei Zheng, Helen Tam, Michaele B. Manigrasso, Joseph G. VerbalisAbstract:The renal vasopressin V2 receptor (V2R) plays a critical role in physiological and pathophysiological processes associated with arginine vasopressin (AVP)-induced Antidiuresis. Because clinical data suggests that females may be more prone to hyponatremia from AVP-mediated Antidiuresis, we investigated whether there are sex differences in the expression and function of the renal V2R. In normal Sprague-Dawley rat kidneys, V2R mRNA and protein expression was 2.6- and 1.7-fold higher, respectively, in females compared with males. To investigate the potential physiological implications of this sex difference, we studied changes in urine osmolality induced by the AVP V2R agonist desmopressin. In response to different doses of desmopressin, there was a graded increase in urine osmolality and decrease in urine volume during a 24-h infusion. Females showed greater mean increases in urine osmolality and greater mean decreases in urine volume at 0.5 and 5.0 ng/h infusion rates. We also studied renal escape from Antidiuresis produced by water loading in rats infused with desmopressin (5.0 ng/h). After 5 days of water loading, urine osmolality of both female and male rats escaped to the same degree physiologically, but V2R mRNA and protein in female kidneys was reduced to a greater degree (−63% and −73%, respectively) than in males (−32% and −48%, respectively). By the end of the 5-day escape period, renal V2R mRNA and protein expression were reduced to the same relative levels in males and females, thereby abolishing the sex differences in V2R expression seen in the basal state. Our results demonstrate that female rats express significantly more V2R mRNA and protein in kidneys than males, and that this results physiologically in a greater sensitivity to V2R agonist administration. The potential pathophysiological implications of these results are that females may be more susceptible to the development of dilutional hyponatremia because of a greater sensitivity to endogenously secreted AVP.
-
whole body volume regulation and escape from Antidiuresis
2006Co-Authors: Joseph G. VerbalisAbstract:Both individual cells and organs regulate their volume in response to sustained hypo-osmolality via solute and water losses. Similar processes occur in the whole body to regulate the volumes of extracellular fluid (ECF) and intravascular spaces toward normal levels. Body water losses occur via the phenomena "escape from Antidiuresis"; solute losses occur through the secondary natriuresis induced by water retention. As a result of resistance to arginine vasopressin (AVP) signaling, escape from Antidiuresis is caused by downregulation of kidney aquaporin-2 expression despite high AVP plasma levels. Recent data have implicated downregulation of vasopressin V2R as a potential mechanism of resistance, and suggest that this may be a result of decreased intrarenal angiotensin II signaling in combination with increased intrarenal nitric oxide and prostaglandin E2 signaling. The natriuresis that results in volume regulation of the ECF and vascular spaces is the result of intrarenal hemodynamic changes produced by volume expansion, but the degree to which these effects are modulated by aldosterone secretion and the activity of distal sodium cotransporters and channels remains to be elucidated. The clinical implication of these volume-regulatory processes is that the chronic hyponatremic state is one of water retention and solute losses from intracellular fluid and ECF compartments. The degree to which solute losses versus water retention contribute to hyponatremia will vary in association with many factors, including the etiology of the hyponatremia, the rapidity of development of the hyponatremia, the chronicity of the hyponatremia, the volume of daily water loading, and individual variability. Understanding these volume-regulatory processes allows a better understanding of many aspects of the conundrum of patients with "clinical euvolemia" and dilutional hyponatremia from AVP-induced water retention.
-
synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin induced Antidiuresis
2003Co-Authors: Takashi Murase, Ying Tian, Xiao Ying Fang, Joseph G. VerbalisAbstract:Recent results from our laboratories indicate that renal escape from AVP-induced Antidiuresis is accompanied by marked downregulation of kidney aquaporin-2 (AQP2) and AVP V2 receptors. The present ...
Takashi Murase - One of the best experts on this subject based on the ideXlab platform.
-
synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin induced Antidiuresis
2003Co-Authors: Takashi Murase, Ying Tian, Xiao Ying Fang, Joseph G. VerbalisAbstract:Recent results from our laboratories indicate that renal escape from AVP-induced Antidiuresis is accompanied by marked downregulation of kidney aquaporin-2 (AQP2) and AVP V2 receptors. The present ...
-
kidney aquaporin 2 expression during escape from Antidiuresis is not related to plasma or tissue osmolality
1999Co-Authors: Takashi Murase, Mark A. Knepper, Carolyn A. Ecelbarger, Erin A Baker, Ying Tian, Joseph G. VerbalisAbstract:Recent results indicate that renal escape from vaso- pressin-induced Antidiuresis is accompanied by a marked downregulation of whole kidney aquaporin-2 (AQP-2) protein and mRNA expression. However, in those studies, the escaped animals were also markedly hypo-osmolar compared to con- trols as a result of water loading during Antidiuresis. The present studies evaluated whether systemic or local osmolality contributes to the downregulation of AQP-2 expression in this model. In the first study, two groups of 1-deamino-(8-D-argi- nine)-vasopressin (dDAVP)-infused rats were water-loaded; after establishment of escape, one group was then water- restricted fo r4dt oreverse the escape, whereas the other group continued daily water loading. Whole kidney AQP-2 protein was measured by Western blotting, and inner medulla AQP-2 mRNA was determined by Northern blotting. Results were compared to dDAVP-infused rats fed solid chow. Afte r4do f water restriction, urine volume decreased to the same level as in the rats on solid chow; however, plasma sodium concentra- tions and plasma osmolality remained low. Despite mainte- nance of significant hypo-osmolality, rats in which escape was subsequently reversed by water restriction reestablished high dDAVP-stimulated kidney levels of AQP-2 afte r4do fwater restriction. In the second study, AQP-2 expression was evaluated in different regions of kidneys from water-loaded rats undergoing escape from Antidiuresis. Despite markedly different interstitial osmolalities, significant downregulation of AQP-2 expression compared to dDAVP-infused control rats was seen in the inner medulla, outer medulla, and cortex. Thus, neither systemic nor interstitial osmolality appears to appreciably be correlated with downregulation of kidney AQP-2 expression during escape from Antidiuresis. These results therefore suggest that addi- tional vasopressin- and osmolality-independent factors, likely related to the effects of extracellular fluid volume expansion, also regulate kidney AQP-2 expression in rats.
-
Studies of renal aquaporin-2 expression during renal escape from vasopressin-induced Antidiuresis.
1998Co-Authors: Joseph G. Verbalis, Soren Nielsen, Takashi Murase, Carolyn A. Ecelbarger, Mark A. KnepperAbstract:In animal models of the syndrome of inappropriate Antidiuresis (SIADH), sustained administration of vasopressin and water results in free-water retention and progressive hyponatremia for several days, which is then followed by escape from the vasopressin-induced Antidiuresis. With the onset of vasopressin escape, water excretion increases despite sustained administration of vasopressin, allowing water balance to be re-established and the serum sodium to be stabilized at a steady, albeit decreased, level. Studies from our laboratories have investigated whether this escape phenomenon can be attributed to altered regulation of aquaporin water channels. After four-day pre-treatment with ldeamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic minipump, rats were divided into control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load) groups. A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating escape from Antidiuresis. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein(measured by semi-quantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. Additional studies have indicated that the observed down-regulation of aquaporin-2 expression also occurs in the renal cortex as well as the inner and outer medullas, and can be reversed simply by water restriction despite maintenance of hyponatremia. Our results therefore suggest that escape from vasopressin-induced Antidiuresis is attributable, at least in part, to a vasopressin-independent and osmolality-independent decrease in aquaporin-2 water channel expression in the renal collecting duct. Similar mechanisms likely contribute to the phenomenon of escape from Antidiuresis seen clinically in patients with SIADH as well.
-
role of renal aquaporins in escape from vasopressin induced Antidiuresis in rat
1997Co-Authors: Carolyn A. Ecelbarger, Mark A. Knepper, Soren Nielsen, Takashi Murase, Beatriz Olson, E A Baker, Joseph G. VerbalisAbstract:The purpose of this study was to investigate whether escape from vasopressin-induced Antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semiquantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. The results suggest that escape from vasopressin-induced Antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin-2 water channel expression in the renal collecting duct.
Mark A. Knepper - One of the best experts on this subject based on the ideXlab platform.
-
kidney aquaporin 2 expression during escape from Antidiuresis is not related to plasma or tissue osmolality
1999Co-Authors: Takashi Murase, Mark A. Knepper, Carolyn A. Ecelbarger, Erin A Baker, Ying Tian, Joseph G. VerbalisAbstract:Recent results indicate that renal escape from vaso- pressin-induced Antidiuresis is accompanied by a marked downregulation of whole kidney aquaporin-2 (AQP-2) protein and mRNA expression. However, in those studies, the escaped animals were also markedly hypo-osmolar compared to con- trols as a result of water loading during Antidiuresis. The present studies evaluated whether systemic or local osmolality contributes to the downregulation of AQP-2 expression in this model. In the first study, two groups of 1-deamino-(8-D-argi- nine)-vasopressin (dDAVP)-infused rats were water-loaded; after establishment of escape, one group was then water- restricted fo r4dt oreverse the escape, whereas the other group continued daily water loading. Whole kidney AQP-2 protein was measured by Western blotting, and inner medulla AQP-2 mRNA was determined by Northern blotting. Results were compared to dDAVP-infused rats fed solid chow. Afte r4do f water restriction, urine volume decreased to the same level as in the rats on solid chow; however, plasma sodium concentra- tions and plasma osmolality remained low. Despite mainte- nance of significant hypo-osmolality, rats in which escape was subsequently reversed by water restriction reestablished high dDAVP-stimulated kidney levels of AQP-2 afte r4do fwater restriction. In the second study, AQP-2 expression was evaluated in different regions of kidneys from water-loaded rats undergoing escape from Antidiuresis. Despite markedly different interstitial osmolalities, significant downregulation of AQP-2 expression compared to dDAVP-infused control rats was seen in the inner medulla, outer medulla, and cortex. Thus, neither systemic nor interstitial osmolality appears to appreciably be correlated with downregulation of kidney AQP-2 expression during escape from Antidiuresis. These results therefore suggest that addi- tional vasopressin- and osmolality-independent factors, likely related to the effects of extracellular fluid volume expansion, also regulate kidney AQP-2 expression in rats.
-
Studies of renal aquaporin-2 expression during renal escape from vasopressin-induced Antidiuresis.
1998Co-Authors: Joseph G. Verbalis, Soren Nielsen, Takashi Murase, Carolyn A. Ecelbarger, Mark A. KnepperAbstract:In animal models of the syndrome of inappropriate Antidiuresis (SIADH), sustained administration of vasopressin and water results in free-water retention and progressive hyponatremia for several days, which is then followed by escape from the vasopressin-induced Antidiuresis. With the onset of vasopressin escape, water excretion increases despite sustained administration of vasopressin, allowing water balance to be re-established and the serum sodium to be stabilized at a steady, albeit decreased, level. Studies from our laboratories have investigated whether this escape phenomenon can be attributed to altered regulation of aquaporin water channels. After four-day pre-treatment with ldeamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic minipump, rats were divided into control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load) groups. A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating escape from Antidiuresis. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein(measured by semi-quantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. Additional studies have indicated that the observed down-regulation of aquaporin-2 expression also occurs in the renal cortex as well as the inner and outer medullas, and can be reversed simply by water restriction despite maintenance of hyponatremia. Our results therefore suggest that escape from vasopressin-induced Antidiuresis is attributable, at least in part, to a vasopressin-independent and osmolality-independent decrease in aquaporin-2 water channel expression in the renal collecting duct. Similar mechanisms likely contribute to the phenomenon of escape from Antidiuresis seen clinically in patients with SIADH as well.
-
role of renal aquaporins in escape from vasopressin induced Antidiuresis in rat
1997Co-Authors: Carolyn A. Ecelbarger, Mark A. Knepper, Soren Nielsen, Takashi Murase, Beatriz Olson, E A Baker, Joseph G. VerbalisAbstract:The purpose of this study was to investigate whether escape from vasopressin-induced Antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semiquantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. The results suggest that escape from vasopressin-induced Antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin-2 water channel expression in the renal collecting duct.
Stefan Silbernagl - One of the best experts on this subject based on the ideXlab platform.
-
evidence for an acid ph in rat renal inner medulla paired measurements with liquid ion exchange microelectrodes on collecting ducts and vasa recta
1994Co-Authors: Ulrich Kersting, D W Dantzler, Hans Oberleithner, Stefan SilbernaglAbstract:We reevaluated the pH in the renal medulla in rats. pH of the vasa recta blood was about 1 pH unit acidic in comparison to the pH of renal artery blood. During furosemideinduced diuresis pH of vasa recta blood increased whereas pH of collecting duct urine further decreased. The acidic pH in the rat renal inner medulla during Antidiuresis raises important questions about the source of H+ in inner medulla.
Soren Nielsen - One of the best experts on this subject based on the ideXlab platform.
-
PKD1 Haploinsufficiency Causes a Syndrome of Inappropriate Antidiuresis in Mice
2013Co-Authors: Ali K. Ahrabi, Soren Nielsen, Claudine Serradeil-le Gal, Sara Terryn, Giovanna Valenti, Nathalie Caron, Danielle Raufaste, Shigeo Horie, Jean-marc Verbavatz, Olivier DevuystAbstract:Mutations in PKD1 are associated with autosomal dominant polycystic kidney disease. Studies in mouse models suggest that the vasopressin (AVP) V2 receptor (V2R) pathway is involved in renal cyst progression, but potential changes before cystogenesis are unknown. This study used a noncystic mouse model to investigate the effect of Pkd1 haploinsufficiency on water handling and AVP signaling in the collecting duct (CD). In comparison with wild-type littermates, Pkd1 �/ � mice showed inappropriate Antidiuresis with higher urine osmolality and lower plasma osmolality at baseline, despite similar renal function and water intake. The Pkd1 �/ � mice had a decreased aquaretic response to both a water load and a selective V2R antagonist, despite similar V2R distribution and affinity. They showed an inappropriate expression of AVP in brain, irrespective of the hypo-osmolality. The cAMP levels in kidney and urine were unchanged, as were the mRNA levels of aquaporin-2 (AQP2), V2R, and cAMP-dependent mediators in kidney. However, the (Ser256) phosphorylated AQP2 was upregulated in Pkd1 �/ � kidneys, with AQP2 recruitment to the apical plasma membrane of CD principal cells. The basal intracellular Ca 2 � concentration was significantly lower in isolated Pkd1 �/ � CD, with downregulated phosphorylated extracellular signal–regulated kinase 1/2 and decreased RhoA activity. Thus, in absence of cystic changes, reduced Pkd1 gene dosage is associated with a syndrome of inappropriate Antidiuresis (positive water balance) reflecting decreased intracellula
-
mechanism of Antidiuresis caused by bendroflumethiazide in conscious rats with diabetes insipidus
1998Co-Authors: Lene Gronbeck, Soren Nielsen, David Marples, Sten ChristensenAbstract:1 The mechanism underlying the antidiuretic eAect of thiazide diuretics in diabetes insipidus (DI) is unknown. This study addressed two specific questions: is the reduction in urine flow rate (V) related to a decrease in the delivery of fluid from the pars recta of the proximal tubules (‘distal delivery’), and are there any changes in the expression and/or intracellular distribution of vasopressin stimulated water channels (AQP2) in the collecting ducts, during chronic thiazide-induced Antidiuresis? 2 Nine Brattleboro rats with vasopressin-deficient DI were treated for 5 days with bendroflumethiazide (BFTZ), 9 mg kg 71 day 71 orally, and 9 Brattleboro rats were left untreated. BFTZ-treated DI rats showed a fall in V from *200 to *75 ml day 71 and an increase in urine osmolality from *130 to *400 mosmol kg 71 . 3 BFTZ-induced Antidiuresis was associated with a persistent loss of sodium, but not of potassium. After 5 days of treatment, clearance studies in conscious rats showed a tendency towards decreases in eAective renal plasma flow (77%), GFR (712%) and lithium clearance (CLi; used as marker for distal delivery) (725%), compared with untreated controls, but none of these changes were statistically significant. There was no apparent relationship between CLi and V in BFTZ-treated or untreated DI rats. 4 BFTZ treatment did not change the expression of AQP2 in homogenates of cortex, outer or inner medulla from DI rats, or from normal Long Evans rats. Light and electron microscopic immunocytochemistry revealed no changes in intracellular distribution of AQP2 in principal cells from inner medullary collecting ducts of BFTZ-treated DI rats. 5 We concluded, (i) that although the antidiuretic eAect of BFTZ in rats with DI is associated with a net loss of Na, the decrease in V shows no association with changes in distal delivery, as estimated by CLi. (ii) Antidiuretic treatment with BFTZ does not alter the expression of subcellular distribution of AQP2 water channels in the collecting ducts. The mechanism underlying the chronic Antidiuresis caused by thiazide diuretics in DI remains elusive.
-
Studies of renal aquaporin-2 expression during renal escape from vasopressin-induced Antidiuresis.
1998Co-Authors: Joseph G. Verbalis, Soren Nielsen, Takashi Murase, Carolyn A. Ecelbarger, Mark A. KnepperAbstract:In animal models of the syndrome of inappropriate Antidiuresis (SIADH), sustained administration of vasopressin and water results in free-water retention and progressive hyponatremia for several days, which is then followed by escape from the vasopressin-induced Antidiuresis. With the onset of vasopressin escape, water excretion increases despite sustained administration of vasopressin, allowing water balance to be re-established and the serum sodium to be stabilized at a steady, albeit decreased, level. Studies from our laboratories have investigated whether this escape phenomenon can be attributed to altered regulation of aquaporin water channels. After four-day pre-treatment with ldeamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic minipump, rats were divided into control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load) groups. A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating escape from Antidiuresis. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein(measured by semi-quantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. Additional studies have indicated that the observed down-regulation of aquaporin-2 expression also occurs in the renal cortex as well as the inner and outer medullas, and can be reversed simply by water restriction despite maintenance of hyponatremia. Our results therefore suggest that escape from vasopressin-induced Antidiuresis is attributable, at least in part, to a vasopressin-independent and osmolality-independent decrease in aquaporin-2 water channel expression in the renal collecting duct. Similar mechanisms likely contribute to the phenomenon of escape from Antidiuresis seen clinically in patients with SIADH as well.
-
role of renal aquaporins in escape from vasopressin induced Antidiuresis in rat
1997Co-Authors: Carolyn A. Ecelbarger, Mark A. Knepper, Soren Nielsen, Takashi Murase, Beatriz Olson, E A Baker, Joseph G. VerbalisAbstract:The purpose of this study was to investigate whether escape from vasopressin-induced Antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semiquantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. The results suggest that escape from vasopressin-induced Antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin-2 water channel expression in the renal collecting duct.