Ontogeny of DA1 receptor-mediated natriuresis in the rat: in vivo and in vitro correlations

Am J Physiol. 1992 Sep;263(3 Pt 2):R631-8. doi: 10.1152/ajpregu.1992.263.3.R631.

Abstract

The natriuretic and diuretic effects of dopamine are attenuated in the young. Because dopamine has actions on receptors (e.g., adrenergic, serotonin) other than dopamine, we studied a novel dopamine agonist, pramipexole, which has a selectivity to both DA1 and DA2-receptor subtypes. Intravenous administration of pramipexole resulted in a dose-related (1, 10, and 100 micrograms.kg-1.min-1) increase in urine flow and absolute and fractional sodium excretion and a decrease in mean arterial pressure (MAP) in three groups of rats studied. Pramipexole induced a greater decrease in MAP in 6- to 7- (n = 5) and 9- to 16- (n = 6) than in 3- to 4-wk-old (n = 8) rats; the natriuresis and diuresis were greatest in 12- to 16- and least in 3- to 4-wk-old rats. The renal effects of pramipexole were mainly due to actions at the DA1 receptor, since these effects were completely blocked by the coinfusion of a DA1 antagonist, SKF 83742. To explore further a cause of the attenuated natriuretic effect of pramipexole in the young, we studied the effect of a selective DA1-receptor agonist, fenoldopam, on amiloride-sensitive 22Na+ uptake in renal brush-border membrane vesicles. The 3-s amiloride-sensitive uptake was inhibited (45%) by fenoldopam (5 x 10(-5)M) in 9- to 16- (n = 6) but not in 3- to 4-wk-old (n = 5) rats. These studies suggest that the attenuated natriuretic effect of dopamine in the young is in part due to decreased DA1 action on the brush-border membrane Na(+)-H+ exchanger.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / urine*
  • Animals
  • Animals, Newborn
  • Benzothiazoles
  • Blood Pressure / drug effects
  • Dopamine / pharmacology
  • Dopamine Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics / drug effects
  • Kidney / drug effects
  • Male
  • Natriuresis* / drug effects
  • Pramipexole
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 / physiology*
  • Thiazoles / pharmacology
  • Time Factors

Substances

  • Benzothiazoles
  • Dopamine Agents
  • Receptors, Dopamine D1
  • Thiazoles
  • Pramipexole
  • Dopamine