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

Abstract

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.

Evidence for Pressure‐Independent Sympathetic Modulation of Central Pulse Wave Velocity

“…Observational data demonstrate that arterial stiffening coexists commonly with chronic elevations in basal sympathetic outflow in cardiovascular disease states 12, 13, 14. Similarly, arterial stiffening associated with healthy aging demonstrates similar relative increases in sympathetic outflow,15, 16 though parallel changes in blood pressure occur also 8, 9, 11.…”

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II

“…The exercise pressor reflex arc includes central cardiovascular pathways. ANG II is suggested to elevate sympathetic nerve activity through its influence on central cardiovascular pathways, which contributes to the development of hypertension (2,28). Moreover, this peptide has been reported to activate NADPH oxidases in the central nervous system (57).…”

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

“…Modern lifestyle, a major factor in CVD, is characterized by (1) stressors, which may lead to sympathetic overactivity and more catecholamine release, followed by subsequent cardiovascular damage; 5,27 (2) high niacin intake due to an increased use of meat and niacin-fortified grain products; 13 and (3) sweat gland inactivity (anaphoresis) due to less physical activity, which may decrease excessive niacin elimination, as niacin can be effectively eliminated from the body through the sweating pathway. 8 The latter two factors may contribute to chronic nicotinamide overload (i.e.…”

“…4 Catecholamines, primarily norepinephrine and epinephrine, mediate the cardiovascular effects of the sympathetic nervous system. 5 CVD is frequently associated with increased circulating levels of catecholamines, 6 which is generally attributed to sympathetic overactivity. However, although a decrease in the degradation of catecholamines is expected to contribute to the elevated circulating catecholamines, whether there are changes in the degradation (i.e.…”