title: Effects of "in vivo" administration of baclofen on rat renal tubular function.
abstract: The effects of the in vivo administration of baclofen on renal tubular transport and aquaporin-2 (AQP2) expression were evaluated. In conscious animals kept in metabolic cages, baclofen (0.01-1mg/kg, s.c.) induced a dose-dependent increment in the urine flow rate (UFR) and in sodium and potassium excretion, associated with an increased osmolal clearance (Closm), a diminished urine to plasma osmolality ratio (Uosm/Posm) and a decrease in AQP2 expression. The above mentioned baclofen effects on functional parameters were corroborated by using conventional renal clearance techniques. Additionally, this model allowed the detection of a diminution in glucose reabsorption. Some experiments were performed with water-deprived or desmopressin-treated rats kept in metabolic cages. Either water deprivation or desmopressin treatment decreased the UFR and increased the Uosm/Posm. Baclofen did not change the Uosm/Posm or AQP2 expression in desmopressin-treated rats; but it increased the UFR and diminished the Uosm/Posm and AQP2 expression in water-deprived animals. These results indicate that in vivo administration of baclofen promotes alterations in proximal tubular transport, since glucose reabsorption was decreased. The distal tubular function was also affected. The increased Closm indicates an alteration in solute reabsorption at the ascending limb of the Henle's loop. The decreased Uosm/Posm and AQP2 expression in controls and in water-deprived, but not in desmopressin-treated rats, lead us to speculate that some effect of baclofen on endogenous vasopressin availability could be responsible for the impaired urine concentrating ability, more than any disturbance in the responsiveness of the renal cells to the hormone.
authors.affiliation: Área Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, (2000) Rosario, Santa Fe, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Donato
authors.forename: Gerardo Bruno
authors.initials: GB
authors.lastname: Pisani
authors.forename: Laura
authors.initials: L
authors.lastname: Trumper
authors.forename: Liliana Alicia
authors.initials: LA
authors.lastname: Monasterolo
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D001418:Baclofen / Q000008:administration & dosage* / Q000494:pharmacology*; D003243:Consciousness; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014867:Water / Q000378:metabolism
chemical_list: D051399:Aquaporin 2; D014867:Water; D003894:Deamino Arginine Vasopressin; D001418:Baclofen
keywords: Aquaporin-2; Baclofen; Desmopressin; GABA(B) agonist; Renal tubular function; Water deprivation