Evidence that dopamine-2 mechanisms control renal function.
Dopamine is synthesized by the kidney, and dopamine-2 (DA2) receptors are present in the renal glomerulus. However, no role for DA2 receptors in the kidney has been defined. We investigated the possible role of DA2 receptors in control of renal function by intrarenal infusion of a highly specific DA2 antagonist YM-09151 (YM), in conscious uninephrectomized dogs (n = 5) in metabolic balance at Na intake 40 meq/day. YM infused at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or Na excretion. Administration of YM (infusions from 0.1 to 10.0 pmol.kg-1.min-1) caused a significant dose-dependent diuresis (F = 20.3; P less than 0.001) and natriuresis (F = 35.2; P less than 0.0001) and an increase in glomerular filtration rate (F = 45.4; P less than 0.0001), renal plasma flow (F = 209.3; P less than 0.0001), and filtration fraction (F = 11.2; P less than 0.0001). No significant changes in plasma renin activity, plasma aldosterone concentration, or mean arterial blood pressure occurred with any of the doses of YM infused into the renal artery. Coinfusion of LY-171555, a specific DA2 agonist, at a dose that itself did not affect renal function, completely abrogated the renal hemodynamic and excretory changes induced by YM. The data suggest that dopamine produced intrarenally may act at renal vascular and/or glomerular DA2 receptors to control renal function.
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; D014150:Antipsychotic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D004285:Dogs; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009392:Nephrectomy; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D012079:Renal Circulation / Q000187:drug effects
D014150:Antipsychotic Agents; D001549:Benzamides; D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D019257:Quinpirole; C030265:nemonapride