Effect of inhibition of MAO and COMT on intrarenal dopamine and serotonin and on renal function.
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 micromol/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 micromol/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.
Wang
Y
Y
Departments of Medicine and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Berndt
T J
TJ
Gross
J M
JM
Peterson
M A
MA
So
M J
MJ
Knox
F G
FG
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D004298:Dopamine / Q000032:analysis / Q000652:urine*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D017551:Microdialysis; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000032:analysis / Q000652:urine*; D012964:Sodium / Q000378:metabolism
D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D010710:Phosphates; D012701:Serotonin; D012964:Sodium; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine