The Eye of the Needle: Redox Mechanisms of Acupuncture Effects in Hypertension

See related article, pp 356–365 Possible roles of oxidative stress and oxidant sources such as Nox nicotinamide adenine dinucleotide phosphate oxidases in the pathogenesis of human hypertension remain yet inconclusive, despite extensive investigation, while antioxidant clinical trials have been mostly negative.1 Although Noxes and mitochondrial dysfunction indeed amplify vascular dysfunction and inflammation in hypertension, their precise role in blood pressure (BP) regulation has been hard to pinpoint.1 This uncertainty reflects the complex mechanisms linking disrupted redox signaling to BP control, making it hard to put together the numerous relevant redox target(s). Meanwhile, an emerging relevant site of redox signaling integration is the central nervous system (CNS). Central neurogenic processes integrating afferent systemic input signals with efferent autonomic regulation are crucial for disturbed cardiovascular regulation in hypertension. Increased sympathetic nervous activity associates with most forms of hypertension, including essential hypertension.2 The rostral ventrolateral medulla (RVLM) is the most important node integrating afferent signals from distinct CNS areas into barosensitive efferent signals to preganglionic neurons.2 Most RVLM neurons are glutamatergic and some adrenergic. A major upstream RVLM connector is the nucleus of the solitary tract, which receives projections from several afferent sensory pathways including baroreceptors, heart mechanoreceptors, and spinal cord, responsive to physical, metabolic, and chemical variables. Enhanced sympathetic outflow via RVLM underlies neurogenic hypertension as a short- or long-term BP regulator.2 Previous work showed that disrupted redox regulation of the RVLM and interconnected structures underlies neurogenic hypertension. RVLM oxidative stress via mitochondria or Noxes1 supports neurogenic hypertension secondary to angiotensin-II infusion or in the spontaneously hypertensive rat (SHR).3 Analogous results were shown for the subfornical organ or the whole AV3V area (the …