Burning Redoxstats in the Brainstem
Lack of Nrf2 and the Rise of Hypertension
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See related article, pp 1198–1206
The most altruistic and sustainable philosophies fail
before the brute brain stem imperative of self-interest
—Peter Watts, Blindsight
Hypertension is a serial killer, and for most, a silent and slow one. Abnormalities in the autonomic control of cardiovascular functions are central factors in hypertension pathogenesis. Blood-borne signals originating from baroreceptors and chemoreceptors can additionally feedback to the central nervous system, regulating autonomic output, via structures that lack a normal blood–brain barrier—such as the subfornical organ, organum vasculosum of the lamina terminalis, and area postrema. These critical, central controllers of autonomic function then communicate with other regions of the central nervous system, such as the hypothalamic and medullary autonomic centers, via efferent neural projections. Most of these autonomic alterations originate from the ventrolateral medulla oblongata, namely within the pressor region of the rostral ventrolateral medulla (RVLM). This longitudinal nucleus contains subsets of sympathetic premotor neurons that preferentially, or even exclusively, regulate sympathetic outflow directed to the heart or blood vessels. On stimulation, these neuronal units increase arterial pressure and heart rate (HR) and are readily silenced when blood pressure raises, coinciding with the abolition of sympathetic nerve activity. Although this region of the brain stem senses pressor signals from the periphery or central regions, such as the hypothalamus or amygdala, RVLM neurons can in fact receive autocrine, paracrine, and endocrine influences. These chemosensory signals are key in the regulation of arterial pressure, myocardial function, and salt and water balance and, thus, contributing to overall cardiovascular homeostasis. RVLM neurons, along with the paraventricular nucleus of the hypothalamus, can be targeted by acute excitatory influences, such as tumor necrosis factor-α infusion, thereby increasing arterial blood pressure, HR, and renal sympathetic nerve activity (RSNA).1 Importantly, in response to tumor necrosis factor-α or other chemosensory stimuli, RVLM neurons can …