Norepinephrine stimulates the epithelial Na+ channel in cortical collecting duct cells via α2-adrenoceptors

Morag K Mansley, Winfried Neuhuber, Christoph Korbmacher, Marko Bertog

Research output: Contribution to journalArticlepeer-review

Abstract

There is good evidence for a causal link between excessive sympathetic drive to the kidney and hypertension. We hypothesized that sympathetic regulation of tubular Na(+) absorption may occur in the aldosterone-sensitive distal nephron, where the fine tuning of renal Na(+) excretion takes place. Here, the appropriate regulation of transepithelial Na(+) transport, mediated by the amiloride-sensitive epithelial Na(+) channel (ENaC), is critical for blood pressure control. To explore a possible effect of the sympathetic transmitter norepinephrine on ENaC-mediated Na(+) transport, we performed short-circuit current (Isc) measurements on confluent mCCDcl1 murine cortical collecting duct cells. Norepinephrine caused a complex Isc response with a sustained increase of amiloride-sensitive Isc by ∼44%. This effect was concentration dependent and mediated via basolateral α2-adrenoceptors. In cells pretreated with aldosterone, the stimulatory effect of norepinephrine was reduced. Finally, we demonstrated that noradrenergic nerve fibers are present in close proximity to ENaC-expressing cells in murine kidney slices. We conclude that the sustained stimulatory effect of locally elevated norepinephrine on ENaC-mediated Na(+) absorption may contribute to the hypertensive effect of increased renal sympathetic activity.

Original languageEnglish
Pages (from-to)F450-F458
JournalAmerican Journal of Physiology - Renal Physiology
Volume308
Issue number5
Early online date17 Dec 2014
DOIs
Publication statusPublished - 1 Mar 2015

Keywords

  • Aldosterone
  • Animals
  • Cell Line
  • Epithelial Sodium Channels
  • Kidney Tubules, Collecting
  • Mice, Inbred C57BL
  • Norepinephrine
  • Receptors, Adrenergic, alpha-2
  • Sodium

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