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

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Item Type:	Article
Title:	Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice
Creators Name:	Sausbier, M., Arntz, C., Bucurenciu, I., Zhao, H., Zhou, X.B., Sausbier, U., Feil, S., Kamm, S., Essin, K., Sailer, C.A., Abdullah, U., Krippeit-Drews, P., Feil, R., Hofmann, F., Knaus, H.G., Kenyon, C., Shipston, M.J., Storm, J.F., Neuhuber, W., Korth, M., Schubert, R., Gollasch, M. and Ruth, P.
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. METHODS AND 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.
Keywords:	Blood pressure, Ion channels, Vasoconstriction, Vasodilation, Hyperaldosteronism, Animals, Mice
Source:	Circulation
ISSN:	0009-7322
Publisher:	American Heart Association
Volume:	112
Page Range:	60-68
Date:	5 July 2005
Official Publication:	https://doi.org/10.1161/01.CIR.0000156448.74296.FE
PubMed:	View item in PubMed

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