title: Effects of NH4Cl intake on renal growth in rats: role of MAPK signalling pathway.
abstract: BACKGROUND
  There is a surprising lack of experimental data on the mechanisms of NH4Cl-induced chronic metabolic acidosis which causes kidney hypertrophy. The NH4Cl treatment results in an absolute increase in kidney mass. Despite findings to indicate a close interaction between NH4Cl-induced chronic metabolic acidosis and renal enlargement, the role of the stimulated serine kinase cascade, mediated by the stepwise activation of extracellular signal-regulated kinase (ERK) signalling, on kidney hypertrophy has not yet been investigated.
  
  
  METHODS
  To test this hypothesis, the present study was undertaken to further explore the possible involvement of mitogen-activated protein kinase (MAPK) signalling pathway in renal growth in chronic NH4Cl-treated rats by western blot analysis.
  
  
  RESULTS
  Our major findings are as follows: (1) Urinary sodium excretion significantly increased during the early phases of NH4Cl-induced acidosis, (2) This occurrence is associated with sustained renal hypertrophy, and (3) sustained basal phosphorylation of IRS-1, Shc, and MAPK/ERKs in acidotic kidneys.
  
  
  CONCLUSIONS
  The present study confirms that NH4Cl-induced acidosis causes disturbances in renal sodium handling. In addition, these findings demonstrate a sustained pre-stimuli activation of kidney MAPK/ERKs signalling pathways in the NH4Cl-treated rats that may correlate with an increased rate of kidney hypertrophy and a transient renal tubule inability to handle sodium. Thus, the altered renal electrolyte handling may result from a reciprocal relationship between the level of renal tubule metabolic activity and ion transport. In addition, the study shows that the appropriate regulation of tyrosine kinase protein phosphorylation, and its downstream signal transduction pathway, plays an important role on renal growth in the NH4Cl-treated rats.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Ciências Medicas, Universidade Estadual de Campinas, 13083-100 Campinas, SP, Brazil.
authors.forename: Leda M A
authors.initials: LM
authors.lastname: Bento
authors.forename: Jose B C
authors.initials: JB
authors.lastname: Carvalheira
authors.forename: Leonardo F
authors.initials: LF
authors.lastname: Menegon
authors.forename: Mario J A
authors.initials: MJ
authors.lastname: Saad
authors.forename: Jose A R
authors.initials: JA
authors.lastname: Gontijo
mesh_terms: D000141:Acidosis, Renal Tubular / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D000643:Ammonium Chloride / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D006984:Hypertrophy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D000643:Ammonium Chloride; D014443:Tyrosine; D012964:Sodium; D020928:Mitogen-Activated Protein Kinases