title: Intrarenal dopamine production and distribution in the rat. Physiological control of sodium excretion.
abstract: Dopamine (DA), produced by the renal proximal tubule, has been demonstrated as an intrarenal paracrine hormone mediating diuresis and natriuresis. The precise mechanism by which DA exerts its cell-to-cell action is not fully understood. In the present study, renal interstitial fluid (RIF) DA (by in vivo microdialysis) and urinary DA excretion (UDAV) were compared in anesthetized rats on either normal (0.28% NaCI, NS) or high (4.0% NaCI, HS) sodium balance and in response to acute gamma-L-glutamyl-L-dopa (gludopa) administration. Urine flow (UV) and sodium excretion (UNaV) in HS were greater than in NS rats. UDAV was increased in HS compared with NS rats. RIF DA was significantly lower in HS than NS rats. Gludopa at 3, 5, and 7.5 nmol/kg (IV bolus) produced a larger increase in UDAV than RIF DA. Only the highest dose of gludopa (7.5 nmol/kg), which resulted in a 7.3-fold increase in UDAV and 1.7-fold increase in RIF DA, was associated with significant diuresis and natriuresis. Cortical and medullary blood flow remained unchanged after gludopa (7.5 nmol/kg) administration, while angiotensin II (100 ng.kg-1.min-1) induced significant reduction in cortical and medullary blood flow. Prior bilateral renal denervation did not have a significant effect on basal DA levels (RIF DA and UDAV) or gludopa-induced DA production or natriuresis and diuresis. These data demonstrated that both chronic sodium loading and acute gludopa administration stimulated renal DA production and release predominantly into the tubule lumen, where DA had a direct tubule action in the control of UNaV. Renal DA production and its renal effects were not significantly regulated by renal sympathetic nerve activity.
authors.affiliation: Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: H M
authors.initials: HM
authors.lastname: Siragy
authors.forename: R A
authors.initials: RA
authors.lastname: Felder
authors.forename: R M
authors.initials: RM
authors.lastname: Carey
mesh_terms: D000818:Animals; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis*; D005260:Female; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D017551:Microdialysis; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
chemical_list: D011355:Prodrugs; D017673:Sodium Chloride, Dietary; C017342:gamma-glutamyl DOPA; D004295:Dihydroxyphenylalanine; D012964:Sodium; D004298:Dopamine