Role of chronic inhibition of dopamine-metabolizing enzymes in the regulation of renal sodium and phosphate excretion in the rat remnant kidney.
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.
Sampaio-Maia
Benedita
B
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Moreira-Rodrigues
Mónica
M
Pestana
Manuel
M
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*
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