Effects of dopamine DA1-receptor blockade and angiotensin converting enzyme inhibition on the renal actions of fenoldopam in the anaesthetized dog.
Experiments were performed in anaesthetized dogs to characterize the renal effects of the selective dopamine DA1-receptor agonist, fenoldopam. Intrarenal artery infusion of fenoldopam (0.01-10 micrograms/kg per min) caused dose-related renal vasodilation. At low doses (0.01-0.3 micrograms/kg per min), renal vasodilation occurred without concomitant falls in blood pressure but was accompanied by increased urine output. This diuresis was most probably a result of reduced tubular reabsorption since glomerular filtration rate was not increased. Both fenoldopam-induced renal vasodilation and diuresis were blocked to a similar extent by the selective dopamine DA1-receptor antagonist, SCH 23390 (30 micrograms/kg, intravenously), suggesting that both effects were mediated by dopamine DA1-receptors. In the presence of the angiotensin converting enzyme inhibitor, captopril (1 mg/kg, intravenously, + 20 micrograms/kg per min, intrarenal artery), fenoldopam (0.01-0.3 micrograms/kg per min) significantly increased fractional excretion of sodium, despite reducing blood pressure; neither of these effects were observed in captopril-free dogs. These observations support the view that the inhibitory effect of fenoldopam on tubular function, and its vasodepressor activity, may be opposed by angiotensin II resulting from fenoldopam-induced renin release.
Department of Peripheral Pharmacology, Glaxo Group Research Limited, Ware, Hertfordshire, UK.
K L
KL
Clark
A
A
Hilditch
M J
MJ
Robertson
G M
GM
Drew
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D018818:Fenoldopam; D007668:Kidney / Q000187:drug effects*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D000804:Angiotensin II; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D018818:Fenoldopam