DA-1 receptors mediate renal effects of the dopamine prodrug, gludopa, in conscious rabbits.
1. Eight male rabbits were implanted with Doppler flow probes around the lower abdominal aorta and left renal artery. A 2 week recovery period was allowed prior to the experiment. 2. Normal saline, gludopa at 25 micrograms/kg per min and at 100 micrograms/kg per min were each infused i.v. for 60 min. One week later the same protocol was administered to four of these animals in addition to DA-1 antagonist SCH 23390 (0.3 mg/kg i.v.) before gludopa infusion. 3. Gludopa elicited significant increases in urine flow, urinary sodium excretion and renal blood flow, and decreased renal vascular resistance. These changes were abolished by the DA-1 antagonist. Blood pressure, heart rate and hindlimb blood flow remained unchanged. 4. Urine dopamine excretion was increased 1200-fold and 7800-fold after gludopa administration at 25 micrograms/kg per min and 100 micrograms/kg per min, respectively, while plasma dopamine concentration and plasma renin activity (PRA) were not significantly altered. However, PRA was elevated by gludopa with DA-1 antagonism. 5. The renal vasodilation, natriuresis and diuresis produced by gludopa in conscious rabbits appears to be mediated by locally generated dopamine via DA-1 receptors.
Wang
Z Q
ZQ
Monash University Department of Medicine, Clayton, Victoria, Australia.
Way
D
D
Trigg
L
L
McGrath
B P
BP
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018492:Dopamine Antagonists; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011355:Prodrugs / Q000494:pharmacology*; D011817:Rabbits; D011954:Receptors, Dopamine / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D001552:Benzazepines; D018492:Dopamine Antagonists; D011355:Prodrugs; D011954:Receptors, Dopamine; C017342:gamma-glutamyl DOPA; D004295:Dihydroxyphenylalanine