Neuronal Networks in Hypertension

Abstract

<jats:p>Neurogenic hypertension is associated with excessive sympathetic nerve activity to the kidneys and portions of the cardiovascular system. Here we examine the brain regions that cause heightened sympathetic nerve activity in animal models of neurogenic hypertension, and we discuss the triggers responsible for the changes in neuronal activity within these regions. We highlight the limitations of the evidence and, whenever possible, we briefly address the pertinence of the findings to human hypertension. The arterial baroreflex reduces arterial blood pressure variability and contributes to the arterial blood pressure set point. This set point can also be elevated by a newly described cerebral blood flow-dependent and astrocyte-mediated sympathetic reflex. Both reflexes converge on the presympathetic neurons of the rostral medulla oblongata, and both are plausible causes of neurogenic hypertension. Sensory afferent dysfunction (reduced baroreceptor activity, increased renal, or carotid body afferent) contributes to many forms of neurogenic hypertension. Neurogenic hypertension can also result from activation of brain nuclei or sensory afferents by excess circulating hormones (leptin, insulin, Ang II [angiotensin II]) or sodium. Leptin raises blood vessel sympathetic nerve activity by activating the carotid bodies and subsets of arcuate neurons. Ang II works in the lamina terminalis and probably throughout the brain stem and hypothalamus. Sodium is sensed primarily in the lamina terminalis. Regardless of its cause, the excess sympathetic nerve activity is mediated to some extent by activation of presympathetic neurons located in the rostral ventrolateral medulla or the paraventricular nucleus of the hypothalamus. Increased activity of the orexinergic neurons also contributes to hypertension in selected models.</jats:p>

Quadruple abnormal protein aggregates in brainstem pathology and exogenous metal-rich magnetic nanoparticles (and engineered Ti-rich nanorods). The substantia nigrae is a very early target in young urbanites and the gastrointestinal tract a key brainstem portal

“…We are documenting in a collection of 186 brainstems from Mexico City residents age 27.29±11.8y old, the striking overlap of hyperphosphorylated tau, ɑ synuclein and TDP-43-markers of AD and PD-, and, surprisingly, transactive response DNA-binding protein TDP-43 (a marker for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-TDP) [89][90][91][92][93][94][95][96] strongly supporting a common denominator impacting the brain early in life. The brainstem and cerebellum are critical not only because they host key networks modulating autonomic function, arousal, motor control and emotions, [64][65][66][67]97 but because damage to specific nuclei and network connections shed light on associated early clinical manifestations and critical portals of entry of our culprit: metal-rich exogenous nanoparticles. 98 The dominant presence of Fe, Al and Ti in the NPs present in substantia nigrae (SN) mitochondria, points unequivocally to their exogenous sources -including engineered Ti-rich nanorods-, and raising serious concerns.…”

Downregulation of M Current Is Coupled to Membrane Excitability in Sympathetic Neurons Before the Onset of Hypertension

“…Sympathetic hyperactivity is known to contribute to the pathophysiology of a variety of cardiovascular diseases, including hypertension, myocardial infarction, and heart failure, although the cellular mechanisms responsible for this have not been fully elucidated. 1 , 2 In hypertension, increased cardiac sympathetic drive is linked to the development of left ventricular hypertrophy 3 and subsequent heart failure, which are independent predictors of mortality. 4 …”

Interplay between baroreflex sensitivity, obesity and related cardiometabolic risk factors (Review)

“…Subsequently, in order to buffer these variations in blood pressure, changes in the SNA are regulated. In patients with hypertension, baroreceptors are dysfunctional and are not able to protect against the constantly elevated blood pressure ( 75 ).…”