Dopamine regulation of renal Na+,K(+)-ATPase activity is lacking in Dahl salt-sensitive rats.
Dopamine is a natriuretic hormone that acts by inhibiting tubular Na+, K(+)-ATPase activity by activation of the dopamine-1 receptor (the thick ascending limb [TAL] of Henle) or by a synergistic effect of dopamine-1 and dopamine-2 receptors (the proximal tubule). The dopamine-1 receptor is coupled to adenylate cyclase. In this article we show that prehypertensive Dahl salt-sensitive (DS) rats have a blunted natriuretic response to dopamine determined during euvolemic conditions compared with Dahl salt-resistant (DR) rats. Furthermore, we have examined the renal tubular effects of dopamine in DS and DR rats. Basal Na+,K(+)-ATPase activity was similar in DS and DR rats. In proximal tubule, dopamine (10(-5) M) inhibited Na+,K(+)-ATPase activity in DR but not in DS rats. The dopamine-2 agonist LY171555 (10(-5) M) together with dibutyryl cyclic AMP (10(-6) M) inhibited proximal tubule Na+,K(+)-ATPase activity in both DS and DR rats. LY171555 alone had no effect. In TAL, the dopamine-1 agonist fenoldopam (10(-5) M) inhibited Na+,K(+)-ATPase activity in DR but not in DS rats. Dibutyryl cyclic AMP (10(-5) M) inhibited TAL Na+,K(+)-ATPase activity in both DS and DR rats. In cell suspensions from the cortex and the medulla, activation of the dopamine-1 receptor significantly increased cyclic AMP content in DR but not in DS rats. The results indicate that DS rats lack the capacity to inhibit tubular Na+,K(+)-ATPase activity because of a defective dopamine-1 receptor adenylate cyclase coupling. This defect may contribute to the impaired natriuretic capacity in DS rats.
Nishi
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A
Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
Eklöf
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AC
Bertorello
A M
AM
Aperia
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D018818:Fenoldopam; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000201:enzymology; D008138:Loop of Henle / Q000201:enzymology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D011954:Receptors, Dopamine / Q000502:physiology; D012016:Reference Values; D012965:Sodium Chloride / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D012965:Sodium Chloride; D003994:Bucladesine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D018818:Fenoldopam; D004298:Dopamine