Inhibition of tubuloglomerular feedback by the D1 agonist fenoldopam in chronically salt-loaded rats.
1. Chronic dietary NaCl loading in rats is paralleled by an increase of the dopamine concentration in the tubular fluid and humorally mediated inhibition of the tubuloglomerular feedback mechanism at the macula densa. Since these two phenomena are causally linked, the alterations in the tubuloglomerular feedback response by the luminal application of dopamine, the D1 agonist fenoldopam, the D2 agonist bromocriptine and the D1 and D2 antagonists SCH 23390 and metoclopramide were further investigated using the micropuncture technique. 2. Very similar, concentration-dependent inhibition of the tubuloglomerular feedback response was observed for dopamine and fenoldopam. Half-maximal inhibition was achieved at 10(-11) M and the slope factors of the sigmoid concentration-response curves were comparable. Bromocriptine was ineffective. 3. The inhibition of TGF by both agonists could be antagonized very similarly and concentration dependently by the D1 antagonist SCH 23390. At equimolar concentrations of 10(-9) M the inhibition was reduced by approximately 50%. Raising the SCH 23390 concentration to 10(-6) M completely abolished the TGF inhibition. In contrast, TGF inhibition by 10(-9) M-fenoldopam or dopamine was not significantly affected by an equimolar concentration of the D2 antagonist metoclopramide. Increasing metoclopramide concentration to 10(-6) M attenuated tubuloglomerular feedback inhibition by approximately 55%. 4. It is concluded that the inhibition of tubuloglomerular feedback seen during chronic dietary salt loading can be ascribed to the binding of endogenous dopamine to luminal D1 receptors on the macula densa cells.
Physiologisches Institut, Universität München, Germany.
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DA
Häberle
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B
Königbauer
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005246:Feedback / Q000187:drug effects; D018818:Fenoldopam; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary / Q000008:administration & dosage
D001552:Benzazepines; D015259:Dopamine Agents; D012982:Sodium, Dietary; D001971:Bromocriptine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam; D008787:Metoclopramide