title: Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance Ca(2+) -activated K(+) channels.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  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 (KCa 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
  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 KCa 1.1 channels.
authors: Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors: Y C
authors: YC
authors: Xu
authors: Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors: S W S
authors: SW
authors: Leung
authors: Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors: G P H
authors: GP
authors: Leung
authors: Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors: R Y K
authors: RY
authors: Man
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D044949:Kaempferols / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D044949:Kaempferols; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009599:Nitroprusside; D009569:Nitric Oxide; C006552:kaempferol; D001920:Bradykinin
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