DIFFERENT RENAL EFFECTS OF 2 INHIBITORS OF CATECHOL-O-METHYLATION IN THE RAT - ENTACAPONE AND CGP-28014

Dopamine is a natriuretic hormone that is abundantly synthesized in th e kidney and is involved in sodium homeostasis. It is metabolized by m onoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) to for m 3-methoxytyramine and dihydroxyphenylacetic acid (DOPAC) and finally homovanillic acid (HVA). In order to investigate whether dopamine met abolism is involved in renal sodium regulation, we tested the renal ef fects of the nitrocatechol entacapone (COMT inhibitor), in comparison with those of the pyridine derivative CGP 28014, in the anaesthetized rat. Entacapone injection resulted in a more than 5-fold increase in s odium excretion, while the renal excretion of dopamine only transientl y increased by 20%. DOPAC excretion showed a more than 2-fold increase which persisted throughout the study. Pretreatment with the selective dopamine DA(1)-receptor antagonist SCH23390 reduced the entacapone-in duced natriuretic response by 69%. Glomerular filtration rate (GFR) an d mean arterial blood pressure (MAP) remained unchanged. injection of CGP 28014 did not produce a natriuretic response: nevertheless, both d opamine and DOPAC excretion increased by 78% and more than 2-fold, res pectively. GFR and MAP remained unchanged. in conclusion, COMT inhibit ion using entacapone results in a mainly DA(1) receptor mediated natri uresis involving inhibition of tubular transport processes, supporting a role for dopamine metabolism in sodium homeostasis. Although CGP 28 014 increases the renal excretion of both dopamine and DOPAC it does n ot affect renal sodium handling indicating a different mechanism of ac tion.