title: Intrarenal dopamine D1-like receptor stimulation induces natriuresis via an angiotensin type-2 receptor mechanism.
abstract: We explored the effects of direct renal interstitial stimulation of dopamine D(1)-like receptors with fenoldopam, a selective D(1)-like receptor agonist, on renal sodium excretion and angiotensin type-2 (AT(2)) receptor expression and cellular distribution in rats on a high-sodium intake. In contrast to vehicle-infused rats, sodium excretion increased in fenoldopam-infused rats during each of three 1-hour experimental periods (<0.001). Blood pressure was unaffected by vehicle or fenoldopam. In plasma membranes of renal cortical cells, fenoldopam increased D(1) receptor expression by 38% (P<0.05) and AT(2) receptor expression by 69% (P<0.01). In plasma membranes of renal proximal tubule cells, fenoldopam increased AT(2) receptor expression by 108% (P<0.01). In outer apical membranes of proximal tubule cells, fenoldopam increased AT(2) receptor expression by 59% (P<0.01). No significant change in total AT(2) receptor protein expression was detectable in response to fenoldopam. Fenoldopam-induced natriuresis was abolished when either PD-123319, a specific AT(2) receptor antagonist, or SCH-23390, a potent D(1)-like receptor antagonist, was coinfused with F (P<0.001). In summary, direct renal D(1)-like receptor activation increased urinary sodium excretion and the plasma membrane expression of AT(2) receptors in renal cortical and proximal tubule cells. D(1)-like receptor-induced natriuresis was abolished by intrarenal AT(2) receptor inhibition. These findings suggest that dopaminergic regulation of sodium excretion involves recruitment of AT(2) receptors to the outer plasma membranes of renal proximal tubule cells and that dopamine-induced natriuresis requires AT(2) receptor activation.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Salomone
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Howell
authors.forename: Helen E
authors.initials: HE
authors.lastname: McGrath
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Kemp
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Keller
authors.forename: John J
authors.initials: JJ
authors.lastname: Gildea
authors.forename: Robin A
authors.initials: RA
authors.lastname: Felder
authors.forename: Robert M
authors.initials: RM
authors.lastname: Carey
mesh_terms: D000758:Anesthesia; D000804:Angiotensin II / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004231:Diuresis / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018818:Fenoldopam / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D009318:Natriuresis / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism / Q000502:physiology*; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D017447:Receptors, Dopamine D1; D012982:Sodium, Dietary; D000804:Angiotensin II; C073402:PD 123319; D018818:Fenoldopam