Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice

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 cyt...

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Published in:	Circulation (New York, N.Y.) Vol. 112; no. 1; pp. 60 - 68
Main Authors:	SAUSBIER, Matthias, AMTZ, Claudia, ABDULLAH, Usamah, KRIPPEIT-DREWS, Peter, FEIL, Robert, HOFMANN, Franz, KNAUS, Hans-Günier, KENYON, Chris, SHIPSTON, Michael J, STORM, Johan F, NEUHUBER, Winfried, KORTH, Michael, BUCURENCIU, Iancu, SCHUBERT, Rudolf, GOLLASCH, Maik, RUTH, Peter, HONG ZHAO, ZHOU, Xiao-Bo, SAUSBIER, Ulrike, FEIL, Susanne, KAMM, Simone, ESSIN, Kyrill, SAILER, Claudia A
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 05-07-2005
Subjects:	Adrenal Cortex - physiology Animals Arteries - physiology Biological and medical sciences Blood and lymphatic vessels Blood Pressure Brain Cardiology. Vascular system Cardiovascular system Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Electrophysiology Homeostasis Hyperaldosteronism - etiology Hypertension - etiology Investigative techniques of hemodynamics Investigative techniques, diagnostic techniques (general aspects) Large-Conductance Calcium-Activated Potassium Channels - deficiency Large-Conductance Calcium-Activated Potassium Channels - physiology Medical sciences Mice Mice, Knockout Miscellaneous Myocytes, Smooth Muscle - physiology Pharmacology. Drug treatments Potassium - blood Vasoconstriction Vasodilation Endocrinopathy Adrenal cortex diseases Hyperaldosteronism Rodentia Vasoconstriction Cardiovascular disease Hyperadrenocorticism Vasodilation ion channels Vasomotricity Vertebrata Mammalia Mouse Animal Adrenal gland diseases Arterial pressure Blood pressure Hemodynamics
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Summary:	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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-7322 1524-4539
DOI:	10.1161/01.CIR.0000156448.74296.FE