Changing dopaminergic activity through different pathways: consequences for renal sodium excretion, regional blood flow and oxygen tension in the rat

Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeo stasis, but the regulation of renal dopaminergic tonus is unclear. We evalu ated different pathways for elevating DA tonus to determine which are impor tant for the ability of the kidney to produce natriuresis and studied the a ccompanying effects on regional renal blood flow and oxygen tension. Thus, we compared the effects of a catechol-O-methyl transferase (COMT)-inhibitor , an unspecific monoamine oxidase (MAO)-inhibitor, a D-1-like receptor agon ist and a DA precursor in anaesthetized rats. Sodium excretion increased si xfold after COMT inhibition, eightfold after administration of the D-1-like agonist, whereas it was similar to control after MAO inhibition and infusi on of DA precursor. Urinary dopamine excretion increased 42% by COMT inhibi tion, 55% by MAO inhibition and 12-fold after DA precursor, but remained un changed after infusion of the D-1-like agonist. The D-1-like receptor agoni st led to a 38% increase in the cortical blood flow and a 21% increase in o uter medullary blood flow. Regional renal blood flow was unaffected by all other treatments. Cortical and outer medullary oxygen tension was unaffecte d in all treatment groups. To conclude, the natriuretic and haemodynamic pr operties of an elevation in DA tonus depends on the route by which the elev ation occurred. Systemic administration of a D-1-like receptor agonist, res ults in a natriuretic response which, as opposed to the natriuresis seen af ter COMT inhibition, coincides with an increase in renal cortical and outer medullary blood flow. Precursor delivery or MAO inhibition did not change neither urinary sodium excretion nor renal blood flow.