gamma-L-Glutamyl-
L-dopa (
gludopa) is a
dopamine (DA)
prodrug with a high degree of renal selectivity. We compared the acute renal effects of
gludopa in conscious control rabbits (n = 6) and rabbits with
doxorubicin-induced
congestive heart failure (CHF, n = 5).
Normal saline and
gludopa 25 and 100 micrograms/kg/min were infused intravenously (i.v.), each for 60 min. One week later, the same protocol was followed except that the DA-1 antagonist
SCH 23390 was given i.v. in a dose of 0.3 mg/kg 10 min before
gludopa infusion. An additional control group (n = 6) received the DA-1 antagonist alone and saline vehicle infusion throughout the study period. In both control and CHF groups,
gludopa elicited significant and similar increases in urine flow (70, 62%),
sodium excretion (127, 98%), and renal blood flow (RBF) (33, 27%), and decreased renal vascular resistance (RVR) (-23, -38%). All these changes were abolished by previous DA-1 antagonism with
SCH 23390. Blood pressure (BP), heart rate (HR), and hindlimb blood flow (HBF) remained unchanged during
gludopa infusion in both groups. In the control group, but not in the CHF group, plasma
renin activity (PRA) increased during
gludopa infusion; this was not influenced by DA-1 antagonism. In normal rabbits (n = 6), treatment with
SCH 23390 alone had no significant effect on renal excretory function or haemodynamics. During
gludopa administration, plasma DA concentration was not significantly altered, whereas urine DA excretion and renal DA content were markedly increased. Intrarenal conversion of
gludopa to DA was significantly less in CHF rabbits as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)