There is growing evidence that the CNS contributes to the development and maintenance of many forms of human hypertension. The disease is typically associated with an elevated sympathetic nerve activity (SNA) and is often satisfactorily controlled by sympatholytic drugs.
The mechanism by which SNA elevates resting blood pressure (BP) is not completely understood, but is thought to involve a resetting of the renal barostat (relationship between BP and sodium excretion).
Several subsets of sympathetic efferent regulate the circulation. The efferents that are most crucial to BP control are tonically active at rest, and their defining property is a powerful feedback inhibition of arterial baroreceptor origin (barosensitive efferents). These sympathetic efferents respond in parallel fashion to many stimuli but can also be differentially regulated according to their visceral target (for example, the heart versus the kidney).
Barosensitive efferents are recruited to raise BP and cardiac output in keeping with behaviour, but their mean level of activity at rest probably has the greatest influence on the 24-h average BP level. This basal activity is generated by a network of brainstem and hypothalamic neurons that converge at several crucial nodal points — the nucleus of the solitary tract (NTS), the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus of the hypothalamus (PVH).
This network is regulated by somatic and visceral sensory afferents and by blood-borne factors (for example, sodium, oxygen, hormones and cytokines), osmolality and pH. These influence selected populations of neurons via circumventricular organs, transendothelial coupling or by simple diffusion.
The RVLM contains adrenergic and other neurons that are the principle source of excitatory drive to the barosensitive sympathetic preganglionic neurons. These neurons have a key role in short-term BP stabilization via the baroreflex, and in coordinating the circulation with respiration.
The PVH also regulates the basal activity of barosensitive sympathetic efferents via parvocellular neurons that project to the RVLM, the NTS and the spinal cord. These neurons are especially important in the context of blood volume and regulation of sodium concentrations.
Sympathetic nerve hyperactivity is commonly mediated by an elevated discharge of the sympathoexcitatory neurons located in the RVLM and PVH, but the root cause of these changes can be remote. For example, increased SNA and neurogenic hypertension can be caused by dysfunction of sensory afferents, such as chemoreceptors, baroreceptors and renal afferents, inappropriately high concentrations of hormones that regulate blood volume and sodium concentration via the hypothalamus–sympathetic nervous system axis, brainstem hypoxaemia or oxidative stress due to hyperactivity of the brain renin–angiotensin system.
Hypertension — the chronic elevation of blood pressure — is a major human health problem. In most cases, the root cause of the disease remains unknown, but there is mounting evidence that many forms of hypertension are initiated and maintained by an elevated sympathetic tone. This review examines how the sympathetic tone to cardiovascular organs is generated, and discusses how elevated sympathetic tone can contribute to hypertension.
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This work was supported by grants from the National Institutes of Health, Heart, Lung and Blood Institute (P.G.G.).
The author declares no competing financial interests.
Autonomic neurons that have their cell bodies in the brainstem or spinal cord and synapse onto visceral motor neurons (sympathetic or parasympathetic) in peripheral ganglia.
Reflex decrease in sympathetic nerve activity that is initiated by the activation of stretch-sensitive afferents located in the arterial wall.
- Renin–angiotensin system
This is a regulated biochemical pathway with paracrine function that leads to the production of angiotensin II and related bioactive peptides in the brain. This system is active in most brain regions that regulate the sympathetic outflow and is activated in various forms of hypertension and heart failure, although the causes of its activation are still not clear.
Sodium excretion by the kidney.
A drug that reduces SNA by a CNS or peripheral action or reduces transmission between sympathetic ganglionic neurons and their peripheral targets.
Neurons located in the brainstem and innervating neurons in the spinal cord, such as sympathetic preganglionic neurons.
- Sympathoexcitatory reflex
Any reflex that causes an increase in SNA (the opposite is a sympathoinhibitory reflex).
- Vigilance-regulating network
Network of neurons that regulate the sleep–wake cycle. This network includes the suprachiasmatic and other hypothalamic nuclei and various brainstem aminergic cell groups.
Reflex elicited by the activation of the carotid bodies (by hypoxia and hypercapnia) or central chemoreceptors (by hypercapnia).
- Sinoaortic denervation
Surgical procedure consisting of sectioning the nerves that contain arterial baroreceptor afferents (principally the carotid sinus nerve and the aortic nerve).
- Hepatoportal osmoreceptors
Sensory afferents located close to the liver that detect changes in osmolality in the blood exiting the digestive system.
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