Sympathetic Nervous System Overactivity and Its Role in the Development of Cardiovascular Disease

2010 ◽  
Vol 90 (2) ◽  
pp. 513-557 ◽  
Author(s):  
Simon C. Malpas
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Multiple Time Scales ◽  
Multiple Time ◽  
Humoral Factors ◽  
Organ Specific ◽  
The Central Nervous System ◽  
Sympathetic Nervous ◽  
Differential Control

This review examines how the sympathetic nervous system plays a major role in the regulation of cardiovascular function over multiple time scales. This is achieved through differential regulation of sympathetic outflow to a variety of organs. This differential control is a product of the topographical organization of the central nervous system and a myriad of afferent inputs. Together this organization produces sympathetic responses tailored to match stimuli. The long-term control of sympathetic nerve activity (SNA) is an area of considerable interest and involves a variety of mediators acting in a quite distinct fashion. These mediators include arterial baroreflexes, angiotensin II, blood volume and osmolarity, and a host of humoral factors. A key feature of many cardiovascular diseases is increased SNA. However, rather than there being a generalized increase in SNA, it is organ specific, in particular to the heart and kidneys. These increases in regional SNA are associated with increased mortality. Understanding the regulation of organ-specific SNA is likely to offer new targets for drug therapy. There is a need for the research community to develop better animal models and technologies that reflect the disease progression seen in humans. A particular focus is required on models in which SNA is chronically elevated.

Central and peripheral mechanisms of arterial pressure lability following baroreceptor denervation

1987 ◽  
Vol 65 (8) ◽  
pp. 1615-1618 ◽  
Author(s):  
R. H. Alper ◽  
H. J. Jacob ◽  
M. J. Brody
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Arterial Pressure ◽  
Humoral Factors ◽  
Neural Transmission ◽  
Sympathetic Transmission ◽  
Sympathetic Nervous ◽  
6 Hydroxydopamine ◽  
Alpha Adrenergic Agonist ◽  
Arterial Pressure Lability

Deafferentation of sinoaortic baroreceptors produces a marked increase in the lability of arterial pressure that is sustained chronically. Studies reviewed in this paper were designed to determine the mechanisms responsible for generating arterial pressure lability. Pharmacological interruption of the humoral vasopressin and angiotensin systems failed to alter arterial pressure lability. In contrast, blockade of sympathetic nervous system transmission at both ganglionic and alpha-adrenergic receptor levels significantly attenuated lability. A similar effect was observed with the peripheral neurotoxin, 6-hydroxydopamine. After blockade of sympathetic transmission, a further reduction in lability was produced by blocking the renin–angiotensin or vasopressin systems. The dissociation of the level of arterial pressure from lability was achieved with parachloroamphetamine which raised arterial pressure but reduced lability. A substantial peripheral contribution to lability was obtained in experiments in which the alpha-adrenergic agonist, phenylephrine, produced a marked increase in lability in both normal and baroreceptor-denervated animals in which humoral and neural transmission were blocked. These data demonstrate that following baroreceptor deafferentation, arterial pressure lability is produced primarily by the sympathetic nervous system and secondarily by circulating humoral factors that appear to act on vascular smooth muscle to induce fluctuations in the level of arterial pressure.

The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management

2010 ◽  
Vol 108 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Murray Esler
Keyword(s):  
Heart Failure ◽  
Nervous System ◽  
Heart Disease ◽  
Essential Hypertension ◽  
Sympathetic Nervous System ◽  
Clinical Translation ◽  
Organ Specific ◽  
Circulatory Control ◽  
Sympathetic Nervous ◽  
Renal Sympathetic

Sympathetic nervous system responses typically are regionally differentiated, with activation in one outflow sometimes accompanying no change or sympathetic inhibition in another. Regional sympathetic activity is best studied in humans by recording from postganglionic sympathetic efferents (multiunit or single fiber recording) and by isotope dilution-derived measurement of organ-specific norepinephrine release to plasma (regional “norepinephrine spillover”). Evidence assembled in this review indicates that sympathetic nervous system abnormalities are crucial in the development of cardiovascular disorders, notably heart failure, essential hypertension, disorders of postural circulatory control causing syncope, and “psychogenic heart disease,” heart disease attributable to mental stress and psychiatric illness. These abnormalities involve persistent, adverse activation of sympathetic outflows to the heart and kidneys in heart failure and hypertension, episodic or ongoing cardiac sympathetic activation in psychogenic heart disease, and defective sympathetic circulatory reflexes in disorders of postural circulatory control. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this “mechanisms-to-management” transition is at differing stages of development with the different conditions. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to introduction of β-adrenergic blockers, an effective therapy. With essential hypertension, perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on demonstration of activation of the renal sympathetic outflow. With psychogenic heart disease and postural syncope syndromes, knowledge of the neural pathophysiology is emerging, but clinical translation remains for the future.

The Role of Noradrenaline and other Transmitter Hormones in the Pathogenesis of Hypertension

1976 ◽  
Vol 51 (s3) ◽  
pp. 427s-430s
Author(s):  
W. J. Louis ◽  
B. Jarrott ◽  
A. E. Doyle
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Essential Hypertension ◽  
Sympathetic Nervous System ◽  
Radioenzymatic Assay ◽  
The Central Nervous System ◽  
Serotonin Turnover ◽  
Mesenteric Vessels ◽  
Sympathetic Nervous

1. Studies with a sensitive radioenzymatic assay for plasma noradrenaline suggest there is a selective overactivity of the sympathetic nervous system in essential hypertension. 2. Serotonin turnover in the mesenteric vessels is approximately twice that of noradrenaline and it is suggested that serotonin may interact with noradrenaline to maintain vascular resistance. 3. Methodology which allows the study of local sympathetic turnover in nuclei of the central nervous system and in peripheral blood vessels is described. This approach has been used to study non-innervated sympathetic turnover observed in phaeochromocytoma.

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