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

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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.