title: DA-1 receptors mediate renal effects of the dopamine prodrug, gludopa, in conscious rabbits.
abstract: 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.
authors.affiliation: Monash University Department of Medicine, Clayton, Victoria, Australia.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Way
authors.forename: L
authors.initials: L
authors.lastname: Trigg
authors.forename: B P
authors.initials: BP
authors.lastname: McGrath
mesh_terms: 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
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D011355:Prodrugs; D011954:Receptors, Dopamine; C017342:gamma-glutamyl DOPA; D004295:Dihydroxyphenylalanine