Evidence that intrarenal dopamine acts as a paracrine substance at the renal tubule.
Dopamine is synthesized within the kidney and dopamine 1 (DA1) receptors are associated with the proximal tubule. In pharmacological doses, dopamine increases renal blood flow and sodium excretion. It is possible that dopamine formed intrarenally acts locally via renal dopamine receptors to control renal function. We investigated the possible paracrine action of renal dopamine by intrarenal administration of a specific DA1 antagonist, Sch 23390, in doses confined to the kidney in conscious uninephrectomized dogs (n = 5) in metabolic balance at a sodium intake of 40 meq/day. Changes (mean +/- SE) in renal excretory and hemodynamic function in response to cumulative infusions of several doses of Sch 23390 (0.01, 0.1, 1.0, 5.0, and 10.0 pmol.kg-1.min-1) were studied. Sch 23390 at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or sodium excretion. Sch 23390 in doses from 0.1 to 10.0 mol.kg-1.min-1 caused a significant dose-dependent antidiuresis (F = 44.9, P less than 0.0001) and antinatriuresis (F = 42.1, P less than 0.0001) and a decrease in fractional sodium excretion (F = 44.2, P less than 0.0001). No changes in estimated renal plasma flow, glomerular filtration rate, plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure occurred with any dose of intrarenal Sch 23390 infused into the renal artery. Rebound diuresis and natriuresis occurred after cessation of the DA1 blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Siragy
H M
HM
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Felder
R A
RA
Howell
N L
NL
Chevalier
R L
RL
Peach
M J
MJ
Carey
R M
RM
D000818:Animals; D001552:Benzazepines / Q000097:blood / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018492:Dopamine Antagonists; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000502:physiology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D012079:Renal Circulation; D014680:Veins
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D004298:Dopamine