Kaempferol enhances endothelium‐dependent relaxation in the porcine coronary artery through activation of large‐conductance Ca 2+ ‐activated K + channels
Background and Purpose Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. Experimental Approach The effect of kaempferol on th...
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Published in | British journal of pharmacology Vol. 172; no. 12; pp. 3003 - 3014 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
01.06.2015
|
Online Access | Get full text |
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Summary: | Background and Purpose
Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle.
Experimental Approach
The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium‐dependent (bradykinin) and ‐independent (sodium nitroprusside) relaxing agents was studied in an
in vitro
organ chamber setup. The whole‐cell patch‐clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (
PCASMCs
).
Key Results
At a concentration without direct effect on vascular tone, kaempferol (3 × 10
−6
M
) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin‐induced relaxation was not affected by
N
ω
‐nitro‐
L
‐arginine methyl ester, an inhibitor of
NO
synthase (10
−4
M
) or
TRAM
‐34 plus
UCL
1684, inhibitors of intermediate‐ and small‐conductance calcium‐activated potassium channels, respectively (10
−6
M
each), but was abolished by tetraethylammonium chloride, a non‐selective inhibitor of calcium‐activated potassium channels (10
−3
M
), and iberiotoxin, a selective inhibitor of large‐conductance calcium‐activated potassium channel (
K
Ca
1.1; 10
−7
M
). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside‐induced relaxations. Kaempferol stimulated an outward‐rectifying current in
PCASMCs
, which was abolished by iberiotoxin.
Conclusions and Implications
The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium‐derived and exogenous
NO
as well as those due to endothelium‐dependent hyperpolarization. This vascular effect of kaempferol involved the activation of
K
Ca
1.1 channels. |
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ISSN: | 0007-1188 1476-5381 |
DOI: | 10.1111/bph.13108 |