So, Mathew J.

The purpose of the present investigation was to study the effects of inhibition of monoamine oxidase (MAO) and/or catechol- O-methyltransferase (COMT), enzymes involved in the degradation of dopamine (DA) and serotonin (5-HT), on intrarenal DA and 5-HT, as reflected in the renal interstitial fluid (RIF) microdialysate and urine, and on renal function. Inhibition of MAO selectively increased RIF 5-HT from 3.16 ± 0.38 to 8.03 ± 1.83 pg/min ( n = 7, P < 0.05), concomitant with decreases in mean arterial blood pressure and glomerular filtration rate (2.09 ± 0.18 to 1.57 ± 0.22 ml/min, n = 7, P < 0.05). Inhibition of COMT significantly increased RIF DA (3.47 ± 0.70 to 8.68 ± 1.96 pg/min, n = 9, P < 0.05), urinary DA (2.00 ± 0.16 to 2.76 ± 0.26 ng/min, n = 9, P < 0.05), and absolute excretion of sodium (6.42 ± 2.00 to 9.82 ± 1.62 μmol/min, n = 10, P < 0.05). Combined inhibition of MAO and COMT significantly increased RIF DA, urinary DA, and urinary 5-HT, which was accompanied with increases in urine flow rate, and absolute (3.03 ± 0.59 to 8.40 ± 1.61 μmol/min, n = 9, P < 0.01) and fractional excretion of sodium. We conclude that inhibition of MAO selectively increases RIF 5-HT. COMT appears to be more important than MAO in the metabolism of intrarenal DA. Physiological increases in intrarenal DA/5-HT induced by inhibition of their degrading enzymes are accompanied with significant alterations of renal function.