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J Physiol. 2014 Jun 15;592(12):2563-74. doi: 10.1113/jphysiol.2014.272880. Epub 2014 Mar 31.

Smooth muscle BK channel activity influences blood pressure independent of vascular tone in mice.

Author information

1
Institut für Neurale Signalverarbeitung, Zentrum für Molekulare Neurobiologie, Falkenried 94, D-20251, Hamburg, Germany Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford, OX1 3QX, UK gregor.sachse@dpag.ox.ac.uk.
2
Institut für Zelluläre und Integrative Physiologie, UKE, Martinistr. 52, D-20246, Hamburg, Germany.
3
Institut für Neurale Signalverarbeitung, Zentrum für Molekulare Neurobiologie, Falkenried 94, D-20251, Hamburg, Germany Institut für Physiologie (Geb 56), Universität des Saarlandes, 66421, Homburg/Saar, Germany.

Abstract

The large conductance voltage- and Ca(2+)-activated K(+) (BK) channel is an important determinant of vascular tone and contributes to blood pressure regulation. Both activities depend on the ancillary BKβ1 subunit. To determine the significance of smooth muscle BK channel activity for blood pressure regulation, we investigated the potential link between changes in arterial tone and altered blood pressure in BKβ1 knockout (BKβ1(-/-)) mice from three different genetically defined strains. While vascular tone was consistently increased in all BKβ1(-/-) mice independent of genetic background, BKβ1(-/-) strains exhibited increased (strain A), unaltered (strain B) or decreased (strain C) mean arterial blood pressures compared to their corresponding BKβ1(+/+) controls. In agreement with previous data on aldosterone regulation by renal/adrenal BK channel function, BKβ1(-/-) strain A mice have increased plasma aldosterone and increased blood pressure. Consistently, blockade of mineralocorticoid receptors by spironolactone treatment reversibly restored the elevated blood pressure to the BKβ1(+/+) strain A level. In contrast, loss of BKβ1 did not affect plasma aldosterone in strain C mice. Smooth muscle-restricted restoration of BKβ1 expression increased blood pressure in BKβ1(-/-) strain C mice, implying that impaired smooth muscle BK channel activity lowers blood pressure in these animals. We conclude that BK channel activity directly affects vascular tone but influences blood pressure independent of this effect via different pathways.

PMID:
24687584
PMCID:
PMC4080938
DOI:
10.1113/jphysiol.2014.272880
[Indexed for MEDLINE]
Free PMC Article

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