title: Decreased abundance of collecting duct aquaporins in post-ischemic renal failure in rats.
abstract: Increased urine flow is often a feature of mild to moderate acute renal failure. This study examines the possible role of dysregulation of collecting duct aquaporins as a factor in this increase. In rats, the left renal pedicle was clamped for 45 min followed by contralateral nephrectomy. Control rats were identical except that the renal pedicle was not clamped. Rats were sacrificed and the kidneys were homogenized at various time points after release of the clamp for semiquantitative immunoblotting of collecting duct aquaporins, as well as the thick ascending limb Na-K-2Cl cotransporter and the proximal tubule water channel, aquaporin-1. Urinary flow rate was significantly increased 18 h after the ischemic insult and remained increased through 72 h. Whole kidney aquaporin-2 protein abundance was 45% of controls at 18 h, 55% of controls at 36 h, and returned to normal 72 h after ischemia. Whole kidney aquaporin-3 protein abundance was 37% of controls at 18 h, 13% of controls at 36 h, and 45% of controls at 72 h. The decline in aquaporin-2 and -3 was confirmed by immunocytochemistry. Abundance of the thick ascending limb Na-K-2Cl cotransporter protein was not significantly decreased. Aquaporin-1 protein abundance was not significantly decreased at 18 h after the ischemic insult, but was significantly reduced after 36 h. Thus, the post-ischemic state is associated with decreased levels of the collecting duct aquaporins, coinciding with an increase in water excretion. It is concluded that decreased aquaporin protein abundance in collecting duct cells is a contributing factor in the increased urine flow seen in moderate post-ischernic acute renal failure.
authors.affiliation: Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1603, USA.
authors.forename: P
authors.initials: P
authors.lastname: Fernández-Llama
authors.forename: P
authors.initials: P
authors.lastname: Andrews
authors.forename: R
authors.initials: R
authors.lastname: Turner
authors.forename: S
authors.initials: S
authors.lastname: Saggi
authors.forename: J
authors.initials: J
authors.lastname: Dimari
authors.forename: T H
authors.initials: TH
authors.lastname: Kwon
authors.forename: S
authors.initials: S
authors.lastname: Nielsen
authors.forename: R
authors.initials: R
authors.lastname: Safirstein
authors.forename: M A
authors.initials: MA
authors.lastname: Knepper
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002498:Centrifugation; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications*; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters; D013997:Time Factors
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D002352:Carrier Proteins; D028021:Sodium-Potassium-Chloride Symporters