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Role of Endothelial Kir in Flow‐Induced Vasodilation via NO Production
Author(s) -
Ahn Sang Joon,
Bian JingTan,
Epshtein Yulia,
Schwab Sarah,
Phillips Shane,
Levitan Irena
Publication year - 2015
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.29.1_supplement.845.13
Subject(s) - vasodilation , production (economics) , flow (mathematics) , cardiology , chemistry , microbiology and biotechnology , medicine , biology , mechanics , physics , economics , macroeconomics
Flow‐induced vasodilation (FIV) regulates vascular tone and homeostasis. A decrease of endothelial‐dependent FIV demonstrates an early indication of endothelial dysfunction. Various other studies suggested that endothelial inwardly‐rectifying K + channels (Kir) are putative flow sensors; however, the role of endothelial Kir in the regulation of vascular tone is unknown. In this study, we show that endothelial Kir plays a key role in FIV via a NO‐dependent mechanism. Briefly, we show that blocking Kir with Ba 2+ or downregulating its activity with a dominant‐negative subunit of Kir2.1 results in significant inhibition of FIV in mouse mesenteric arteries and Kir electrophysiology. FIV is also inhibited in mesenteric arteries isolated from Kir2.1 +/‐ mice. The expression level of Kir2.1 in arterial endothelial cells derived from Kir2.1 +/‐ mice shows significant reduction compared to from WT mice. Without endothelium, Kir2.1 +/‐ and WT mice have no difference in papaverine or SNP induced vasodilation. To test further the mechanism by which Kir regulates FIV, the experiments were performed in the presence of LNAME. As expected, inhibiting NOS reduces FIV in WT arteries, but there is no decrease in arteries from Kir2.1 +/‐ mice. Additionally, flow‐induced NO production is significantly reduced. Taken together these data indicate that Kir channels contribute to FIV by regulating NO release. In contrast, inhibiting Ca 2+ ‐dependent K + channels (SK/IK) had an additive effect to Kir suppression suggesting that SK/IK and Kir regulate FIV by parallel pathways.