Role of kidney dopamine in the natriuretic response to volume expansion in rats.
It has been postulated that endogenously produced dopamine (DA) may play a role in the regulation of renal sodium excretion. In the present study, experiments were designed to test the hypothesis that acute volume expansion with isotonic sodium chloride stimulates the production of DA within the kidney, which in turn acts on specific DA1 receptors to promote sodium excretion. In pentobarbital-anesthetized rats, acute volume expansion over a period of 1 hour evoked a pronounced increase in urine output and urinary sodium excretion. These diuretic and natriuretic effects were not accompanied by any significant changes in blood pressure or heart rate. However, there was a significant elevation in central venous pressure and a transient rise in glomerular filtration rate. The natriuretic and diuretic response was accompanied by a significant increase in urinary DA excretion, and this effect was clearly dissociated from the rise in glomerular filtration rate. In a separate group of rats, the effects of acute volume expansion were studied in the presence of selective DA1 receptor antagonist SCH-23390 (50 micrograms/kg i.v. bolus; 10 micrograms/kg/min). During DA1 receptor blockade, there was a marked attenuation in the diuretic and natriuretic response throughout the period of volume expansion, when compared with that in the control group. The changes in central venous pressure and glomerular filtration rate were identical in the two groups. In another group of rats, the renal effects of exogenously administered DA were studied. DA (0.5 micrograms/kg/min) produced significant increases in urine output and urinary sodium excretion, without causing any alterations in blood pressure or glomerular filtration rate, suggesting a tubular site of action.(ABSTRACT TRUNCATED AT 250 WORDS)
Hegde
S S
SS
Department of Pharmacology, University of Houston, Texas 77204-5515.
Jadhav
A L
AL
Lokhandwala
M F
MF
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002496:Central Venous Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018492:Dopamine Antagonists; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010952:Plasma Substitutes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001552:Benzazepines; D018492:Dopamine Antagonists; D010952:Plasma Substitutes; D004298:Dopamine