title: Effects of exogenous desmopressin on a model of heat stress nephropathy in mice.
abstract: Recurrent heat stress and dehydration have recently been shown experimentally to cause chronic kidney disease (CKD). One potential mediator may be vasopressin, acting via the type 2 vasopressin receptor (V2receptor). We tested the hypothesis that desmopressin accelerates CKD in mice subjected to heat stress and recurrent dehydration. Recurrent exposure to heat with limited water availability was performed in male mice over a 5-wk period, with one group receiving desmopressin two times daily and the other group receiving vehicle. Two additional control groups were not exposed to heat or dehydration and received vehicle or desmopressin. The effects of the treatment on renal injury were assessed. Heat stress and recurrent dehydration induced functional changes (albuminuria, elevated urinary neutrophil gelatinase-associated protein), glomerular changes (mesangiolysis, matrix expansion), and tubulointerstitial changes (fibrosis, inflammation). Desmopressin also induced albuminuria, glomerular changes, and tubulointerstitial fibrosis in normal animals and also exacerbated injury in mice with heat stress nephropathy. Both heat stress and/or desmopressin were also associated with activation of the polyol pathway in the renal cortex, likely due to increased interstitial osmolarity. Our studies document both glomerular and tubulointerstitial injury and inflammation in heat stress nephropathy and may be clinically relevant to the pathogenesis of Mesoamerican nephropathy. Our data also suggest that vasopressin may play a role in the pathogenesis of the renal injury of heat stress nephropathy, likely via a V2receptor-dependent pathway.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Roncal-Jimenez
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
authors.forename: Tamara
authors.initials: T
authors.lastname: Milagres
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
authors.forename: Ana
authors.initials: A
authors.lastname: Andres-Hernando
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
authors.forename: Masanari
authors.initials: M
authors.lastname: Kuwabara
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.|Division of Endocrinology, Metabolism, and Diabetes, University of Colorado, Aurora, Colorado.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.|Division of Endocrinology, Metabolism, and Diabetes, University of Colorado, Aurora, Colorado.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Song
authors.affiliation: Division of Pediatric Endocrinology, University of Colorado, Aurora, Colorado; and.
authors.forename: Petter
authors.initials: P
authors.lastname: Bjornstad
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Garcia
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Laboratory of Renal Physiopathology, INC Ignacio Chávez, Mexico City, Mexico.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sanchez-Lozada
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado; Richard.Johnson@ucdenver.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000419:Albuminuria / Q000139:chemically induced / Q000503:physiopathology; D000449:Aldehyde Reductase / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D003167:Complement Activation / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000633:toxicity*; D003681:Dehydration / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005355:Fibrosis; D005631:Fructokinases / Q000378:metabolism; D018882:Heat Stress Disorders / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D015415:Biomarkers; D017483:Receptors, Vasopressin; D000641:Ammonia; D003404:Creatinine; D000449:Aldehyde Reductase; D005631:Fructokinases; C046173:fructokinase; D003894:Deamino Arginine Vasopressin
keywords: Mesoamerican nephropathy; chronic kidney disease of unknown etiology; copeptin; vasopressin