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Genetic deficit of SK3 and IK1 channels abolishes EDHF‐type vasodilation and elevates blood pressure.
Author(s) -
Koehler Ralf,
Brähler Sebastian,
Kaistha Anuradha,
Woelfle Stephanie,
Kaistha Brajesh P,
Wit Cor,
Wulff Heike,
Adelman John P.,
Hoyer Joachim
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1018.7
Subject(s) - dilator , vasodilation , blood pressure , hyperpolarization (physics) , medicine , endothelium , endothelium derived hyperpolarizing factor , cardiology , endocrinology , potassium channel , chemistry , charybdotoxin , organic chemistry , nuclear magnetic resonance spectroscopy
In blood vessels, the Ca2+‐activated K+ channels SK3 (KCa2.3) and IK1 (KCa3.1) are expressed in the endothelium and their activation has been proposed to play a role in the arteriolar dilation attributed to the action of an "endothelium‐derived hyperpolarizing factor" (EDHF). However, the precise understanding of the roles of SK3 and IK1 channels in the EDHF‐dilator response and in blood pressure control remains incomplete. To clarify the roles of SK3 and IK1 channels in the EDHF‐dilator response, we generated mice deficient of both channels. Here we show that endothelial IK1/SK3 deficiency disrupted smooth muscle hyperpolarization and EDHF signalling in conduit arteries and in resistance arterioles in vivo. As a consequence, SK3/IK1‐deficient mice exhibit elevated arterial blood pressure which is most prominent during physical activity. Over‐expression of SK3 in IK1‐/‐/SK3T/T‐mice partially restores EDHF‐mediated vasodilation and lowers blood pressure. Our study demonstrates that endothelial SK3 and IK1 channels are the major constituents of the EDHF‐pathway in vivo and reveals a significant contribution of the EDHF‐dilator system to arterial blood pressure. Therefore, these endothelial K+‐channels may represent novel therapeutic targets for lowering arterial blood pressure in hypertension.