a Department of Physiology and Pharmacology , Cumming School of Medicine, University of Calgary , Calgary , Alberta , Canada.
Channels (Austin). 2018 Jan 1;12(1):126-136. doi: 10.1080/19336950.2018.1454814.
Endothelial small and intermediate-conductance, Ca-activated K channels (KCa2.3 and KCa3.1, respectively) play an important role in the regulation of vascular function and systemic blood pressure. Growing evidence indicates that they are intimately involved in agonist-evoked vasodilation of small resistance arteries throughout the circulation. Small molecule activators of KCa2.x and 3.1 channels, such as SKA-31, can acutely inhibit myogenic tone in isolated resistance arteries, induce effective vasodilation in intact vascular beds, such as the coronary circulation, and acutely decrease systemic blood pressure in vivo. The blood pressure-lowering effect of SKA-31, and early indications of improvement in endothelial dysfunction suggest that endothelial KCa channel activators could eventually be developed into a new class of endothelial targeted agents to combat hypertension or atherosclerosis. This review summarises recent insights into the activation of endothelial Ca activated K channels in various vascular beds, and how tools, such as SKA-31, may be beneficial in disease-related conditions.
内皮细胞小电导和中电导钙激活钾通道（KCa2.3 和 KCa3.1）在调节血管功能和全身血压方面发挥着重要作用。越来越多的证据表明，它们与整个循环中小阻力动脉激动剂诱导的血管舒张密切相关。KCa2.x 和 3.1 通道的小分子激活剂，如 SKA-31，可以在分离的阻力血管中急性抑制肌源性张力，在完整的血管床（如冠状循环）中诱导有效的血管舒张，并在体内急性降低全身血压。SKA-31 的降压作用和内皮功能障碍改善的早期迹象表明，内皮 KCa 通道激活剂最终可能被开发成一类新的内皮靶向药物，以对抗高血压或动脉粥样硬化。这篇综述总结了最近对各种血管床内皮细胞钙激活钾通道激活的新认识，以及 SKA-31 等工具在相关疾病条件下可能带来的益处。
