Role of Chronic Inhibition of Dopamine-Metabolizing Enzymes in the Regulation of Renal Sodium and Phosphate Excretion in the Rat Remnant Kidney

Abstract

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. 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. 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. 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.