Xu Y C, Leung S W S, Leung G P H, Man R Y K
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Br J Pharmacol. 2015 Jun;172(12):3003-14. doi: 10.1111/bph.13108. Epub 2015 Mar 27.
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.
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).
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.
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.
山奈酚是一种存在于正常人类饮食中的植物黄酮类化合物，可调节血管舒缩张力。本研究旨在阐明该黄酮类化合物增强血管平滑肌舒张的信号通路。
在体外器官浴槽装置中研究了山奈酚对猪冠状动脉对内皮依赖性（缓激肽）和非内皮依赖性（硝普钠）舒张剂舒张作用的影响。采用全细胞膜片钳技术测定山奈酚对猪冠状动脉平滑肌细胞（PCASMCs）钾通道的影响。
在对血管张力无直接影响的浓度下，山奈酚（3×10⁻⁶ M）增强了缓激肽和硝普钠引起的舒张作用。山奈酚对缓激肽诱导舒张的增强作用不受一氧化氮合酶抑制剂N（ω）-硝基-L-精氨酸甲酯（10⁻⁴ M）或分别为中电导和小电导钙激活钾通道抑制剂的TRAM-34加UCL 1684（各10⁻⁶ M）的影响，但被钙激活钾通道的非选择性抑制剂氯化四乙铵（10⁻³ M）和大电导钙激活钾通道（KCa 1.1）的选择性抑制剂iberiotoxin（10⁻⁷ M）所消除。Iberiotoxin也抑制了山奈酚对硝普钠诱导舒张的增强作用。山奈酚刺激了PCASMCs中的外向整流电流，该电流被iberiotoxin消除。
目前的结果表明，在猪冠状动脉平滑肌细胞中，山奈酚增强了内皮源性和外源性一氧化氮引起的舒张以及内皮依赖性超极化引起的舒张。山奈酚的这种血管效应涉及KCa 1.1通道的激活。
