Regulation of dopamine-induced natriuresis by the dopamine-metabolizing enzyme catechol-O-methyltransferase

Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeo stasis. A study was performed to elucidate two possible regulatory pathways of DA-induced natriuresis, i.e., metabolism and precursor delivery. This w as done by use of an intraperitoneal injection of a catechol-O-methyltransf erase (COMT) inhibitor, entacapone, or intravenous infusion of the DA precu rsor, L-dopa. Entacapone (30 mg/kg i.p.) induced a more than fivefold incre ase in renal sodium excrection which occurred without changes in renal haem odynamics. The natriuretic response was highly dependent on DA D-1-like rec eptor activation, since the selective D-1-like receptor antagonist SCH23390 attenuated the natriuretic response by 61%, while the selective D-2-like r eceptor antagonist sulpiride was ineffective. The urinary excretion of DA d id not increase. Infusion of L-dopa (60 mu g/h/kg) only induced a twofold i ncrease in sodium excretion, but the urinary excretion of DA increased more than 17-fold. The L-dopa-induced natriuretic response occurred without inc rements in glomerular filtration rate and could be blocked with the D-1-lik e receptor antagonist SCH23390. It is concluded that the DA-metabolizing en zyme COMT is involved in the regulation of the natriuretic effect of intrar enal DA, It may be speculated that intrarenal DA activity is not primarily determined on the basis of delivered precursor, but on that of the level of DA metabolism.