Functional contribution of the endothelial component to the vasorelaxing effect of resveratrol and NS 1619, activators of the large-conductance calcium-activated potassium channels
Functional contribution of the endothelial component to the vasorelaxing effect of resveratrol and NS 1619, activators of the large-conductance calcium-activated potassium channels
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DOI：
10.1007/s00210-006-0129-3
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Breschi, Maria C.
中科院分区：
文献类型：
--
作者：
Calderone, Vincenzo;Martelli, Alma;Breschi, Maria C.
平滑肌的大电导钙激活钾通道 (BK) 由于其钙依赖性和电压依赖性激活机制，在血管张力的相关调节中发挥作用。内皮细胞培养方法也表明了内皮 BK 通道的潜在作用。然而，尚未报道旨在评估内皮 BK 通道对 BK 开启剂作用的贡献的功能研究。白藜芦醇和 NS 1619（BK 开启剂）已在内皮完整和裸露的主动脉环上进行了测试。此外，还评估了钾通道阻滞剂 TEA（四乙铵）、4-AP（4-氨基吡啶）和 IbTX（伊贝里奥毒素）以及 NO 途径抑制剂（L-NAME 和 ODQ）的高去极化作用。内皮细胞的存在增加了 BK 开启剂的血管舒张效力。 L-NAME 和 ODQ 消除了这种增强作用。 TEA、4-AP、IbTX 和高去极化对内皮剥脱的主动脉环中的白藜芦醇具有适度或没有拮抗作用。 NS 1619 对内皮剥脱的主动脉环的作用不受 IbTX 影响，并被 TEA、4-AP 和高去极化适度拮抗。在完整的内皮血管中，TEA、IbTX 和 4-AP 拮抗两种 BK 激活剂的血管舒张作用。 BK 介导的内皮 NO 释放似乎是一个非常重要的因素，决定了对 BK 开放剂的血管舒张特性的强烈影响。因此，最终使用 BK 开启剂进行治疗可能会促进一系列心血管影响，不仅限于直接的血管舒张作用，而且还归因于内皮 NO 的显着贡献。
Large-conductance calcium-activated potassium channels (BK) of smooth muscle play a role in the relevant modulation of vascular tone, due to their calcium- and voltage-dependent mechanisms of activation. A potential role of endothelial BK channels has also been suggested by approaches on endothelial cell cultures. However, no functional study, aimed at evaluating the contribution of endothelial BK channels to the effect of BK-openers, has been reported. Resveratrol and NS 1619, BK-openers, have been tested on endothelium-intact and -denuded aortic rings. Furthermore, the effects of high depolarisation of potassium channel blockers TEA (Tetraethylammonium), 4-AP ( 4-Aminopyridine) and IbTX (Iberiotoxin) and of inhibitors of NO-pathway (L-NAME and ODQ) have been evaluated. The presence of endothelium increased the vasorelaxing potency of BK-openers. This potentiation was eliminated by L-NAME and ODQ. TEA, 4-AP, IbTX and high depolarisation had modest or no antagonist influence on resveratrol in endothelium-denuded aortic rings. The effects of NS 1619 on endothelium-denuded aortic rings were not affected by IbTX, and were modestly antagonised by TEA, 4-AP and high depolarisation. In intact endothelium vessels, TEA, IbTX and 4-AP antagonised the vasorelaxing effect of the two BK-activators. A BK-mediated release of endothelial NO seems a very important factor, determining a strong influence on vasodilator profile of BK-openers. Therefore, an eventual therapy with a BK-opener could promote a series of cardiovascular impacts not confined to the only direct vasorelaxing effects, but also due to a significant contribution of endothelial NO.