Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice.
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Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice. / Sausbier, Matthias; Arntz, Claudia; Bucurenciu, Iancu; Zhao, Hong; Zhou, Xiao-Bo; Sausbier, Ulrike; Feil, Susanne; Kamm, Simone; Essin, Kyrill; Sailer, Claudia A; Abdullah, Usamah; Krippeit-Drews, Peter; Feil, Robert; Hofmann, Franz; Knaus, Hans-Günther; Kenyon, Chris; Shipston, Michael J; Storm, Johan F; Neuhuber, Winfried; Korth, Michael; Schubert, Rudolf; Gollasch, Maik; Ruth, Peter.
In: CIRCULATION, Vol. 112, No. 1, 1, 2005, p. 60-68.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice.
AU - Sausbier, Matthias
AU - Arntz, Claudia
AU - Bucurenciu, Iancu
AU - Zhao, Hong
AU - Zhou, Xiao-Bo
AU - Sausbier, Ulrike
AU - Feil, Susanne
AU - Kamm, Simone
AU - Essin, Kyrill
AU - Sailer, Claudia A
AU - Abdullah, Usamah
AU - Krippeit-Drews, Peter
AU - Feil, Robert
AU - Hofmann, Franz
AU - Knaus, Hans-Günther
AU - Kenyon, Chris
AU - Shipston, Michael J
AU - Storm, Johan F
AU - Neuhuber, Winfried
AU - Korth, Michael
AU - Schubert, Rudolf
AU - Gollasch, Maik
AU - Ruth, Peter
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 112
SP - 60
EP - 68
JO - CIRCULATION
JF - CIRCULATION
SN - 0009-7322
IS - 1
M1 - 1
ER -