Renal dopamine and tubular DA-1 receptors in the regulation of sodium excretion.
1. We have performed studies in rats with selective DA-1 receptor agonists fenoldopam and dopexamine which show that activation of tubular DA-1 receptors by these agents results in natriuresis and diuresis. 2. In pentobarbital-anaesthetized rats, an acute increase in sodium intake produced by volume expansion (5% body weight) with isotonic sodium chloride led to pronounced increases in sodium and water excretion. These natriuretic and diuretic responses were accompanied by significant increases in urinary dopamine excretion and could be attenuated by the selective DA-1 receptor antagonist, SCH 23390. 3. Intravenous infusion of atrial natriuretic factor produced hypotension, bradycardia and an increase in sodium and water excretion. The natriuretic and diuretic response to the peptide was not accompanied by any changes in urinary dopamine excretion but it was attenuated by SCH 23390 and the dopa decarboxylate inhibitor, carbidopa. 4. These results show that renal tubular DA-1 receptors can be activated by selective agonists, which subsequently leads to natriuresis and diuresis. During acute volume expansion, there is an increased production of renal dopamine, which contributes to the natriuretic response via activation of tubular DA-1 receptors. Finally, we discovered that endogenous dopamine plays a permissive role in the full expression of the renal effects of the atrial natriuretic factor.
Lokhandwala
M F
MF
Department of Pharmacology, University of Houston, Texas 77204-5515.
Vyas
S J
SJ
Hegde
S S
SS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018818:Fenoldopam; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C046318:dopexamine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D009320:Atrial Natriuretic Factor; D018818:Fenoldopam; D004298:Dopamine