标题： 将内皮源性超极化信号整合到微血管疾病的多靶点治疗策略中 显示英文标题

标题： Integrating Endothelial-Derived Hyperpolarizing Signaling into a Multitarget Therapeutic Strategy for Microvascular Disease

摘要： 内皮细胞释放多种血管舒张分子，如一氧化氮和前列环素，以及通过开启钙敏感钾通道诱导血管平滑肌细胞超极化的特定因子。 依赖钾通道的血管舒张在微血管中很常见，并可部分补偿其他血管舒张机制的不足。 增强这种备用血管舒张机制可能有助于治疗微血管疾病，如脑小血管病和子痫前期，这是一种妊娠特异性高血压综合征，其特征是全身性内皮功能障碍。 开发药理学钾通道开放剂遇到了重大挑战，包括特异性问题、安全顾虑和脱靶效应。 本研究批判性地评估了将超极化整合到整体血管舒张策略中的优缺点，以通过单一或联合药物疗法管理缺血性疾病。 显示英文摘要

摘要： Endothelial cells release various vasorelaxing molecules, such as nitric oxide and prostacyclin, along with defined factors that induce hyperpolarization of vascular smooth muscle cells through the opening of calcium-sensitive potassium channels. Potassium channel-dependent vasorelaxation is prevalent in microvessels and can partially compensate for deficiencies in other vasodilatory mechanisms. Enhancing this backup vasorelaxant mechanism may aid the treatment of microvascular disorders, such as cerebral small vessel disease and preeclampsia, a pregnancy-specific hypertensive syndrome, which is characterized by systemic endothelial dysfunction. The development of pharmacological potassium channel openers has encountered significant challenges, including issues of specificity, safety concerns, and off-target effects. This study critically evaluates the advantages and drawbacks of integrating hyperpolarization into a holistic vasorelaxant strategy for managing ischemic disease through single or combination drug therapies.