Intrarenal dopamine-1 receptors control renal function.
Dopamine receptors are classified to DA-1 and DA-2 and are characterized in renal tissue by radioligand binding and by the response of renal adenylate cyclase to dopaminergic agonists and antagonists. DA-1 receptors are localized in the renal tubules, the medial layer of renal microvessels, and the juxtaglomerular apparatus. DA-1 receptor stimulation causes dilation of renal, mesenteric, coronary, and cerebral vessels. In the present study, we tested the hypothesis that dopamine is a paracrine substance in the control of renal function. We employed a potent specific DA-1 receptor antagonist, SCH, to evaluate the role of intrarenal DA-1 receptor in the maintenance of renal function. Intrarenal DA-1 receptor blockade with SCH caused a highly significant dose-dependent antidiuresis and antinatriuresis, and decreased FENa. A rebound diuresis and natriuresis above control values were observed after cessation of DA-1 receptor blockade. There were no changes in renal hemodynamic function during DA-1 receptor blockade. These results strongly suggest that the antinatriuresis and antidiuresis induced by DA-1 receptor blockade are mediated by an action at the renal tubule. The infusion rate of SCH administered intrarenally was sufficiently low to produce no measurable systemic effects including PRA, PAC, and MAP. Thus, these results can be interpreted as due to intrarenal DA-1 blockade. In summary, we have demonstrated that renal excretory function is highly sensitive to DA-1 receptor blockade within the kidney and appears to be mediated by renal tubular events. This study provides strong evidence that DA-1 receptors play a physiological role in the control of 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; D001552:Benzazepines / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D018492:Dopamine Antagonists; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D009318:Natriuresis / Q000187:drug effects; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1