Hypertension of Kcnmb1-/- is linked to deficient K secretion and aldosteronism

P. Richard Grimm, Debra L. Irsik, Deann C. Settles, J. David Holtzclaw, Steven Claude Sansom

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Mice lacking the β1-subunit (gene, Kcnmb1; protein, BK-β1) of the large Ca-activated K channel (BK) are hypertensive. This phenotype is thought to result from diminished BK currents in vascular smooth muscle where BK-β1 is an ancillary subunit. However, the β1-subunit is also expressed in the renal connecting tubule (CNT), a segment of the aldosterone-sensitive distal nephron, where it associates with BK and facilitates K secretion. Because of the correlation between certain forms of hypertension and renal defects, particularly in the distal nephron, it was determined whether the hypertension of Kcnmb1-/- has a renal origin. We found that Kcnmb1-/- are hypertensive, volume expanded, and have reduced urinary K and Na clearances. These conditions are exacerbated when the animals are fed a high K diet (5% K; HK). Supplementing HK-fed Kcnmb1-/- with eplerenone (mineralocorticoid receptor antagonist) corrected the fluid imbalance and more than 70% of the hypertension. Finally, plasma [aldo] was elevated in Kcnmb1 -/- under basal conditions (control diet, 0.6% K) and increased significantly more than wild type when fed the HK diet. We conclude that the majority of the hypertension of Kcnmb1-/- is due to aldosteronism, resulting from renal potassium retention and hyperkalemia.

Original languageEnglish (US)
Pages (from-to)11800-11805
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number28
DOIs
StatePublished - Jul 14 2009

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Hyperaldosteronism
Nephrons
Diet
Hypertension
Kidney
Large-Conductance Calcium-Activated Potassium Channels
Mineralocorticoid Receptor Antagonists
Hyperkalemia
Renal Hypertension
Aldosterone
Vascular Smooth Muscle
Potassium
Phenotype
Proteins

Keywords

  • Adrenal medulla
  • BK
  • Eplerenone
  • Mineralcorticoid
  • Volume expansion

ASJC Scopus subject areas

  • General

Cite this

Hypertension of Kcnmb1-/- is linked to deficient K secretion and aldosteronism. / Grimm, P. Richard; Irsik, Debra L.; Settles, Deann C.; Holtzclaw, J. David; Sansom, Steven Claude.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 28, 14.07.2009, p. 11800-11805.

Research output: Contribution to journalArticle

Grimm, P. Richard ; Irsik, Debra L. ; Settles, Deann C. ; Holtzclaw, J. David ; Sansom, Steven Claude. / Hypertension of Kcnmb1-/- is linked to deficient K secretion and aldosteronism. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 28. pp. 11800-11805.
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