title: Norepinephrine stimulates the epithelial Na+ channel in cortical collecting duct cells via α2-adrenoceptors.
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.
authors.affiliation: Institut für Zelluläre und Molekulare Physiologie and.
authors.forename: Morag K
authors.initials: MK
authors.lastname: Mansley
authors.affiliation: Lehrstuhl für Anatomie I, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Neuhuber
authors.affiliation: Institut für Zelluläre und Molekulare Physiologie and christoph.korbmacher@fau.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Korbmacher
authors.affiliation: Institut für Zelluläre und Molekulare Physiologie and.
authors.forename: Marko
authors.initials: M
authors.lastname: Bertog
mesh_terms: D000450:Aldosterone; D000818:Animals; D002460:Cell Line; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D018341:Receptors, Adrenergic, alpha-2; D000450:Aldosterone; D012964:Sodium; D009638:Norepinephrine
keywords: collecting duct; epithelial Na+ channel; epithelial sodium transport; norepinephrine; renal sympathetic innervation