title: Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice.
abstract: BACKGROUND
  Abnormally elevated blood pressure is the most prevalent risk factor for cardiovascular disease. The large-conductance, voltage- and Ca2+-dependent K+ (BK) channel has been proposed as an important effector in the control of vascular tone by linking membrane depolarization and local increases in cytosolic Ca2+ to hyperpolarizing K+ outward currents. However, the BK channel may also affect blood pressure by regulating salt and fluid homeostasis, particularly by adjusting the renin-angiotensin-aldosterone system.
  
  
  RESULTS
  Here we report that deletion of the pore-forming BK channel alpha subunit leads to a significant blood pressure elevation resulting from hyperaldosteronism accompanied by decreased serum K+ levels as well as increased vascular tone in small arteries. In smooth muscle from small arteries, deletion of the BK channel leads to a depolarized membrane potential, a complete lack of membrane hyperpolarizing spontaneous K+ outward currents, and an attenuated cGMP vasorelaxation associated with a reduced suppression of Ca2+ transients by cGMP. The high level of BK channel expression observed in wild-type adrenal glomerulosa cells, together with unaltered serum renin activities and corticotropin levels in mutant mice, suggests that the hyperaldosteronism results from abnormal adrenal cortical function in BK(-/-) mice.
  
  
  CONCLUSIONS
  These results identify previously unknown roles of BK channels in blood pressure regulation and raise the possibility that BK channel dysfunction may underlie specific forms of hyperaldosteronism.
authors.affiliation: Pharmakologie und Toxikologie, Pharmazeutisches Institut der Universität Tübingen, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Sausbier
authors.forename: Claudia
authors.initials: C
authors.lastname: Arntz
authors.forename: Iancu
authors.initials: I
authors.lastname: Bucurenciu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Zhou
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sausbier
authors.forename: Susanne
authors.initials: S
authors.lastname: Feil
authors.forename: Simone
authors.initials: S
authors.lastname: Kamm
authors.forename: Kyrill
authors.initials: K
authors.lastname: Essin
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Sailer
authors.forename: Usamah
authors.initials: U
authors.lastname: Abdullah
authors.forename: Peter
authors.initials: P
authors.lastname: Krippeit-Drews
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Knaus
authors.forename: Chris
authors.initials: C
authors.lastname: Kenyon
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shipston
authors.forename: Johan F
authors.initials: JF
authors.lastname: Storm
authors.forename: Winfried
authors.initials: W
authors.lastname: Neuhuber
authors.forename: Michael
authors.initials: M
authors.lastname: Korth
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schubert
authors.forename: Maik
authors.initials: M
authors.lastname: Gollasch
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
mesh_terms: D000302:Adrenal Cortex / Q000502:physiology; D000818:Animals; D001158:Arteries / Q000502:physiology; D001794:Blood Pressure; D004594:Electrophysiology; D006706:Homeostasis; D006929:Hyperaldosteronism / Q000209:etiology*; D006973:Hypertension / Q000209:etiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D011188:Potassium / Q000097:blood; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D011188:Potassium