title: Role of chronic inhibition of dopamine-metabolizing enzymes in the regulation of renal sodium and phosphate excretion in the rat remnant kidney.
abstract: OBJECTIVE
  The present study examined the effects of chronic selective or combined inhibition of type A monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) on daily urinary excretion of dopamine and metabolites and on natriuresis and phosphaturia in 3/4 nephrectomized (3/4nx) and Sham rats.
  
  
  METHODS
  The 3/4nx and Sham rats were placed in metabolic cages and received the MAO-A-selective inhibitor Ro-411049 (7.5 mg x kg(-1) bid) and/or the COMT-selective inhibitor BIA 3-202 (30 mg x kg(-1) bid) orally for 3 days during high sodium diet.
  
  
  RESULTS
  Selective COMT inhibition increased the urinary excretion of the deaminated metabolite (3,4-dihydroxyphenylacetic acid, DOPAC) and decreased the urinary excretion of the methylated (3-methoxytyramine, 3-MT) and deaminated plus methylated metabolite (homovanillic acid, HVA) in both groups. Selective MAO-A inhibition increased the urinary excretion of 3-MT and reduced the urinary excretion of both DOPAC and HVA in either 3/4nx or Sham rats. Combined inhibition of MAO-A and COMT did not significantly change the urinary excretion of DOPAC and markedly decreased the urinary excretion of 3-MT and HVA in both groups. Selective or combined inhibition of MAO-A and COMT did not alter the daily urinary excretion of dopamine, sodium or phosphate in either 3/4nx or Sham rats.
  
  
  CONCLUSIONS
  Chronic selective or combined inhibition of MAO-A and COMT is not of major importance in regulating the dopamine-dependent natriuresis and phosphaturia in either 3/4nx or Sham rats.
authors.affiliation: Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
authors.forename: Benedita
authors.initials: B
authors.lastname: Sampaio-Maia
authors.forename: Mónica
authors.initials: M
authors.lastname: Moreira-Rodrigues
authors.forename: Manuel
authors.initials: M
authors.lastname: Pestana
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009392:Nephrectomy; D010710:Phosphates / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine*
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D010710:Phosphates; D015102:3,4-Dihydroxyphenylacetic Acid; D012964:Sodium; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine