NADPH oxidase signaling, blood pressure sensing and the development of myogenic tone

在动态条件下，动脉张力受多种刺激调节，包括神经元活动、组织代谢和血管内压力。一个世纪前，贝利斯首次观察到动脉可以对血压的变化做出反应。“肌源性反应”已在各种血管床中记录，并依赖于平滑肌[Ca 2 +]的升高。升高的压力通过激活信号转导途径增加平滑肌[Ca 2 +]，所述信号转导途径：1）使平滑肌脱钙并提高Ca 2+通道活性;和2）动员内部Ca 2+储存。虽然已经鉴定了一些驱动肌源性张力发展的离子通道，但是使得压力调节成为可能的信号级联还没有。目前的工作通常集中在标准的G-蛋白偶联机制，很少冒险“在这个信号框之外”考虑新的分子。这包括活性氧物质，其产生可以通过NADPH氧化酶（NOX）促进，所述酶已知与机械敏感蛋白质相关。

Under dynamic conditions, arterial tone is regulated by multiple stimuli including neuronal activity, tissue metabolism and intravascular pressure. A century ago, Bayliss first observed that arteries could respond to changes in blood pressure. The “myogenic response” has been documented in various vascular beds and is dependent upon a rise in smooth muscle [Ca2+]. Elevated pressure augments smooth muscle [Ca2+] by activating signal transduction pathways that: 1) depolarize smooth muscle and elevate Ca2+ channel activity; and 2) mobilize internal Ca2+ stores. While some of the ion channels driving myogenic tone development have have been identified, the signaling cascades which enable pressure modulation have not. Present day work typically focuses on standard G-protein coupled mechanisms and few venture “outside this signaling box” to consider novel molecules. This includes reactive oxygen species whose production could be facilitated by NADPH oxidases (NOX), enzymes known to associate with mechanosensitive proteins.