Changing dopaminergic activity through different pathways: consequences for renal sodium excretion, regional blood...

Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis, but the regulation of renal dopaminergic tonus is unclear. We evaluated different pathways for elevating DA tonus to determine which are important for the ability of the kidney to produce natriuresis and studied the accompanying 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 D1-like receptor agonist and a DA precursor in anaesthetized rats. Sodium excretion increased sixfold after COMT inhibition, eightfold after administration of the D1-like agonist, whereas it was similar to control after MAO inhibition and infusion of DA precursor. Urinary dopamine excretion increased 42% by COMT inhibition, 55% by MAO inhibition and 12-fold after DA precursor, but remained unchanged after infusion of the D1-like agonist. The D1-like receptor agonist led to a 38% increase in the cortical blood flow and a 21% increase in outer medullary blood flow. Regional renal blood flow was unaffected by all other treatments. Cortical and outer medullary oxygen tension was unaffected in all treatment groups. To conclude, the natriuretic and haemodynamic properties of an elevation in DA tonus depends on the route by which the elevation occurred. Systemic administration of a D1-like receptor agonist, results in a natriuretic response which, as opposed to the natriuresis seen after 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.