Dopamine1-receptor blockade inhibits ANP-induced phosphaturia and calciuria in rats.
Atrial natriuretic peptide (ANP) is known to enhance the excretion of Pi and Ca, solutes reabsorbed primarily by the proximal tubule. Previous studies have shown that proximal tubule Na transport is inhibited by dopamine (DA), and that the natriuretic action of ANP is blunted by DA-receptor blockade. However, alterations in Na reabsorption cannot localize ANP or DA action to a specific nephron site. Therefore, the possibility that DA mediates the apparent proximal tubule effects of ANP was investigated with the use of Pi and Ca as proximal tubule markers. ANP was infused into normal rats in the presence and absence of specific DA-receptor antagonists, and Na, Pi, and Ca excretion rates were determined. ANP enhanced Na, Pi, and Ca excretion at doses that failed to alter glomerular filtration rate and mean arterial pressure (MAP). DA1-receptor blockade significantly blunted the influence of ANP on urinary Na, Pi, and Ca excretion, whereas DA2-receptor blockade was without effect. MAP and inulin and p-aminohippurate (PAH) clearances remained stable during DA-receptor blockade. Because endogenous ANP levels are elevated in rats with remnant kidneys, and because blockade of endogenous ANP reduces Pi and Ca as well as Na excretion in this model, the effect of DA1-receptor blockade on solute excretion was also examined in rats with 5/6 nephrectomy. DA1-receptor blockade significantly reduced absolute and fractional Na, Pi, and Ca excretion in rats with 5/6 nephrectomy, in the absence of measurable changes in MAP, inulin, or PAH clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Ortola
F V
FV
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts.
Seri
I
I
Downes
S
S
Brenner
B M
BM
Ballermann
B J
BJ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics / Q000652:urine*; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D010710:Phosphates / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012964:Sodium / Q000652:urine
D010710:Phosphates; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D009320:Atrial Natriuretic Factor; D012964:Sodium; D002118:Calcium