The role of dopamine-metabolizing enzymes in the regulation of renal sodium excretion in the rat.
The intrarenal natriuretic hormone dopamine (DA) is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). We have previously shown that inhibition of COMT by entacapone results in a potent D1-like receptor-mediated natriuretic response. The present study was performed using anaesthetized rats to compare the importance of MAO and COMT in DA-mediated natriuresis by use of the MAO inhibitor phenelzine. Urinary sodium and DA excretion remained unchanged after MAO inhibition, while excretion of the main metabolite dihydroxyphenylacetic acid (DOPAC) decreased by 55%. The response was unaltered if 5-hydroxytryptamine receptors (5-HT1A) were blocked during MAO inhibition. We also investigated the specific renal activities of MAO and COMT in rat renal cortex during DA-influenced natriuresis. Specific COMT activity in the renal cortex was reduced by 13% after isotonic sodium loading (5% of body mass) whereas renal MAO-A and MAO-B activities remained unaltered. Furthermore, preliminary data obtained from spontaneously hypertensive rats, whose basal urinary DA excretion is higher than that of normotensive Wistar-Kyoto rats, show a tendency for renal COMT activity to be lower. It is concluded that MAOinhibition by phenelzine does not alter sodium excretion. Furthermore, specific renal cortical COMT activity is reduced during partly D1-like receptor-mediated natriuresis, whereas MAO activity remains unchanged. The results suggest that MAO is less important than COMT in regulating DA-mediated natriuresis in the rat kidney.
Odlind
C
C
Dept of Physiology, University of Uppsala, Biomedical Centre, Sweden. cecilia.odlind@physiology.uu.se
Reenilä
I
I
Männistö
P T
PT
Ekblom
J
J
Hansell
P
P
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007672:Kidney Cortex / Q000201:enzymology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D010624:Phenelzine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000493:pharmacokinetics / Q000652:urine
D008996:Monoamine Oxidase Inhibitors; D012982:Sodium, Dietary; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D010624:Phenelzine; D004298:Dopamine