Redox State Drives the Pathogenesis of Hypertension

17 Obstructive sleep apnea (OSA) is one of the most common causes of hypertension 18 in western societies. OSA causes chronic intermittent hypoxia (CIH) in specialized O 2-19 sensing glomus cells of the carotid body. CIH generates increased reactive oxygen 20 species (ROS) that trigger a feed-forward mechanism in which increased intracellular 21 calcium levels ([Ca 2+ ] i) trigger increased HIF-1α synthesis and increased HIF-2α 22 degradation. As a result, the normal homeostatic balance between HIF-1α-dependent pro-23 oxidant and HIF-2α-dependent anti-oxidant enzymes is disrupted, leading to further 24 increases in ROS. Carotid body sensory nerves project to the nucleus tractus solitarius, 25 from which the information is relayed via interneurons to the rostral ventrolateral medulla 26 in the brainstem, which sends sympathetic neurons to the adrenal medulla to stimulate the 27 release of epinephrine and norepinephrine, catecholamines that increase blood pressure.