title: Kidney aquaporin-2 expression during escape from antidiuresis is not related to plasma or tissue osmolality.
abstract: Recent results indicate that renal escape from vasopressin-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 controls 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-arginine]-vasopressin (dDAVP)-infused rats were water-loaded; after establishment of escape, one group was then water-restricted for 4 d to reverse 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. After 4 d of water restriction, urine volume decreased to the same level as in the rats on solid chow; however, plasma sodium concentrations and plasma osmolality remained low. Despite maintenance of significant hypo-osmolality, rats in which escape was subsequently reversed by water restriction reestablished high dDAVP-stimulated kidney levels of AQP-2 after 4 d of water 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 additional vasopressin- and osmolality-independent factors, likely related to the effects of extracellular fluid volume expansion, also regulate kidney AQP-2 expression in rats.
authors.affiliation: Department of Medicine, Georgetown University, Washington, DC 20007, USA. muraset@medlib.georgetown.edu
authors.forename: T
authors.initials: T
authors.lastname: Murase
authors.forename: C A
authors.initials: CA
authors.lastname: Ecelbarger
authors.forename: E A
authors.initials: EA
authors.lastname: Baker
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.forename: M A
authors.initials: MA
authors.lastname: Knepper
authors.forename: J G
authors.initials: JG
authors.lastname: Verbalis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000032:analysis / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D046508:Culture Techniques; D003894:Deamino Arginine Vasopressin; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation; D005110:Extracellular Space / Q000502:physiology; D007010:Hyponatremia / Q000139:chemically induced / Q000378:metabolism* / Q000652:urine; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D012313:RNA / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents; D012680:Sensitivity and Specificity; D012964:Sodium / Q000097:blood; D014868:Water Deprivation / Q000502:physiology
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D012076:Renal Agents; D012313:RNA; D012964:Sodium; D003894:Deamino Arginine Vasopressin