Evidence from functional and autoradiographic studies for the presence of tubular dopamine-1 receptors and their involvement in the renal effects of fenoldopam.
Evidence from receptor-ligand binding and biochemical studies seems to suggest the possible existence of tubular dopamine DA-1 receptors in the rat kidney. However, it is not yet clear whether these putative tubular DA-1 receptors are involved in the functional renal responses elicited during the administration of DA and DA receptor agonists. In the present study we have examined the renal effects of several doses of selective DA-1 receptor agonist fenoldopam in pentobarbital-anesthetized rats in an attempt to unmask a direct tubular DA-1 receptor-mediated diuresis and natriuresis. Additionally, we have performed receptor-ligand binding and autoradiographic studies to examine the presence and localization of DA-1 receptors in various regions of the rat kidney. At the highest dose studied (2 micrograms/kg/min), fenoldopam produced diuresis and natriuresis, which was accompanied by a significant decrease in blood pressure and also a significant increase in glomerular filtration rate. At 1 micrograms/kg/min, the diuretic and natriuretic effects of fenoldopam were observed in the absence of any changes in blood pressure and glomerular filtration rate, but there was a significant increase in renal blood flow. However, at 0.5 micrograms/kg/min, fenoldopam-induced natriuresis and diuresis was not accompanied by any changes in blood pressure, renal blood flow or glomerular filtration rate, implying a direct tubular effect. These effects of fenoldopam appear to be mediated via activation of DA-1 receptors, because they were antagonized by the selective DA-1 antagonist SCH 23390.(ABSTRACT TRUNCATED AT 250 WORDS)
Hedge
S S
SS
Department of Pharmacology, University of Houston, Texas.
Ricci
A
A
Amenta
F
F
Lokhandwala
M F
MF
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology*; D018818:Fenoldopam; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000032:analysis* / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis* / Q000187:drug effects; D017447:Receptors, Dopamine D1
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam