Title

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

Document Type

Journal Article

Publication Date

1-1-1992

Journal

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volume

263

Issue

3 32-3

DOI

10.1152/ajpregu.1992.263.3.r631

Keywords

fenoldopam; pramipexole; sodium-hydrogen antiporter

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 μg · 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.

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