Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice.
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.
Sausbier
Matthias
M
Pharmakologie und Toxikologie, Pharmazeutisches Institut der Universität Tübingen, Tübingen, Germany.
Arntz
Claudia
C
Bucurenciu
Iancu
I
Zhao
Hong
H
Zhou
Xiao-Bo
XB
Sausbier
Ulrike
U
Feil
Susanne
S
Kamm
Simone
S
Essin
Kyrill
K
Sailer
Claudia A
CA
Abdullah
Usamah
U
Krippeit-Drews
Peter
P
Feil
Robert
R
Hofmann
Franz
F
Knaus
Hans-Günther
HG
Kenyon
Chris
C
Shipston
Michael J
MJ
Storm
Johan F
JF
Neuhuber
Winfried
W
Korth
Michael
M
Schubert
Rudolf
R
Gollasch
Maik
M
Ruth
Peter
P
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
D051036:Large-Conductance Calcium-Activated Potassium Channels; D011188:Potassium