THE DOPAMINE PRODRUG, GLUDOPA, DECREASES BOTH RENAL AND EXTRARENAL NORADRENALINE SPILLOVER IN CONSCIOUS RABBITS

1. Renal and total noradrenaline (NA) spillover rates were examined un der control conditions and during graded infusions of gludopa (gamma-L -glutamyl-L-dopa) in conscious rabbits. 2. Gludopa infusion at 25 and 100 mug/kg per min did not alter mean arterial pressure (MAP) and hear t rate (HR), but had significant dose-related effects on the renal dop amine (DA) system. At the high dose there were pronounced increases in urinary DA excretion (>6000-fold) and renal DA content (>100-fold); r enal NA content doubled. 3. Renal venous DA increased after gludopa in fusion, but arterial plasma DA concentrations were not significantly c hanged. Mean arterial plasma gludopa and L-dopa concentrations reached 890, 3190 ng/mL and 3, 10 ng/mL at low and high doses, respectively. 4. Gludopa resulted in a pronounced dose-dependent fall in renal NA sp illover, which at 100 mug/kg per min accounted for almost half of the reduction in overall NA spillover rate. 5. The significant falls in re nal and extrarenal NA spillover rate during gludopa infusion are consi stent with suppression of renal and overall sympathetic activity. Glud opa-induced inhibition of renal NA spillover is likely to be due to th e actions of DA generated in the kidney on presynaptic DA-2 and alpha- 2 receptors. A central sympathoinhibitory mechanism may explain the re duced total NA spillover.