Sympathetic Nervous Activation in Essential Hypertension

Esler, Murray

doi:10.1161/hypertensionaha.110.151506

Cited by 19 publications

(11 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Neurogenic mechanisms are dominant in the pathogenesis of essential hypertension in ϳ50% of patients (30). Spontaneously hypertensive rats (SHR) or stroke-prone SHR (SHRSP) exhibit increased RSNA during the development of hypertension, and blood pressure and RSNA are positively correlated (52,79).…”

Section: Effects Of No In the Brain System In Experimental Models Of mentioning

confidence: 99%

“…blood pressure; sympathetic nervous system; central nervous system; nitric oxide; oxidative stress ACTIVATION OF THE SYMPATHETIC nervous system is critically involved in the pathogenesis of hypertension, from initial occurrence to the development of target organ damage, such as heart failure, stroke, and renal failure (35,36). The importance of the effects of the renin-angiotensin system on the sympathetic nervous system in the pathogenesis of hypertension is recently highlighted (30,31). This is not surprising because both the autonomic nervous system and hormonal factors are the major regulators of blood pressure; therefore, abnormalities of either system are likely to be involved in the pathogenesis of essential hypertension (30,31,37).…”

mentioning

confidence: 99%

“…The importance of the effects of the renin-angiotensin system on the sympathetic nervous system in the pathogenesis of hypertension is recently highlighted (30,31). This is not surprising because both the autonomic nervous system and hormonal factors are the major regulators of blood pressure; therefore, abnormalities of either system are likely to be involved in the pathogenesis of essential hypertension (30,31,37). Esler (30) reported that the sympathetic nervous system is activated in ϳ50% of patients with hypertension, particularly in patients with essential hypertension.…”

mentioning

confidence: 99%

“…This is not surprising because both the autonomic nervous system and hormonal factors are the major regulators of blood pressure; therefore, abnormalities of either system are likely to be involved in the pathogenesis of essential hypertension (30,31,37). Esler (30) reported that the sympathetic nervous system is activated in ϳ50% of patients with hypertension, particularly in patients with essential hypertension. Central sympathetic outflow is determined by several important nuclei and their circuits in the central nervous system (CNS) (9,81).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Hirooka

Kishi

Sakai

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

109

108

View full text Add to dashboard Cite

Hirooka Y, Kishi T, Sakai K, Takeshita A, Sunagawa K. Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension. Am J Physiol Regul Integr Comp Physiol 300: R818-R826, 2011. First published February 2, 2011 doi:10.1152/ajpregu.00426.2010 and reactive oxygen species (ROS) play important roles in blood pressure regulation via the modulation of the autonomic nervous system, particularly in the central nervous system (CNS). In general, accumulating evidence suggests that NO inhibits, but ROS activates, the sympathetic nervous system. NO and ROS, however, interact with each other. Our consecutive studies and those of others strongly indicate that an imbalance between NO bioavailability and ROS generation in the CNS, including the brain stem, activates the sympathetic nervous system, and this mechanism is involved in the pathogenesis of neurogenic aspects of hypertension. In this review, we focus on the role of NO and ROS in the regulation of the sympathetic nervous system within the brain stem and subsequent cardiovascular control. Multiple mechanisms are proposed, including modulation of neurotransmitter release, inhibition of receptors, and alterations of intracellular signaling pathways. Together, the evidence indicates that an imbalance of NO and ROS in the CNS plays a pivotal role in the pathogenesis of hypertension. blood pressure; sympathetic nervous system; central nervous system; nitric oxide; oxidative stress ACTIVATION OF THE SYMPATHETIC nervous system is critically involved in the pathogenesis of hypertension, from initial occurrence to the development of target organ damage, such as heart failure, stroke, and renal failure (35,36). The importance of the effects of the renin-angiotensin system on the sympathetic nervous system in the pathogenesis of hypertension is recently highlighted (30,31). This is not surprising because both the autonomic nervous system and hormonal factors are the major regulators of blood pressure; therefore, abnormalities of either system are likely to be involved in the pathogenesis of essential hypertension (30,31,37). Esler (30) reported that the sympathetic nervous system is activated in ϳ50% of patients with hypertension, particularly in patients with essential hypertension. Central sympathetic outflow is determined by several important nuclei and their circuits in the central nervous system (CNS) (9, 81). These pathways involve many neurotransmitters and neuromodulators (16,25,38,99). In particular, the brain stem circuitry is now considered crucial for the pathogenesis of hypertension, including both excitatory and inhibitory inputs from the supramedullary nuclei and the baroreceptors (16,25,38,100,115). In this review, we focus on the role of nitric oxide (NO) and reactive oxygen species (ROS) in the brain stem as factors constituting the neural mechanisms of hypertension. Because of the close relationship between NO and ROS, we discuss the individual roles of NO and ROS in the brain stem i...

show abstract

Section: Effects Of No In the Brain System In Experimental Models Of mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Hirooka

Kishi

Sakai

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

109

108

View full text Add to dashboard Cite

show abstract

“…This autonomic dysregulation contributes to increased blood pressure (BP), cardiac arrhythmias and atrial fibrillation, and the resulting progression to heart failure. [8][9][10][11][12][13] Although autonomic imbalance in T2D has been extensively documented, the neural mechanisms underlying the sympathetic hyperactivity involved in high cardiac morbidity and mortality in T2D patients remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Role of brainstem thyrotropin-releasing hormone-triggered sympathetic overactivation in cardiovascular mortality in type 2 diabetic Goto–Kakizaki rats

Yang

Nyby

et al. 2011

Hypertens Res

View full text Add to dashboard Cite

Sympathetic hyperactivity has an important role in cardiovascular mortality in patients with type 2 diabetes (T2D). Thyrotropinreleasing hormone (TRH)-containing fibers innervate autonomic motor and premotor nuclei of the brainstem and spinal cord that regulate cardiovascular functions. We compared cardiovascular responses to application of TRH-analog in the brainstem of Wistar and T2D Goto-Kakizaki (GK) rats. GK rats exhibited basal systolic hypertension (152±2 mm Hg) and had a significantly potentiated, dose-related hypertensive response to intracisternal (i.c.) injection of the TRH-analog RX77368 (10-60 ng). In GK rats only, i.c. RX77368 (30-60 ng) markedly increased heart rate (HR; +88 b.p.m.) and induced acute cardiac mortality (100%), concurrent with extreme hyperglycemia (426 mmol l À1 ), increased plasma H 2 O 2 and 8-isoprostane, and enhanced heart expression of NADPH oxidase 4 and vascular cell adhesion molecule-1 mRNAs. GK rats also had elevated basal plasma epinephrine, higher adrenal gene expression of tyrosine hydroxylase and dopamine b-hydroxylase (DbH), and greater plasma catecholamine and adrenal DbH responses to i.c. TRH-analog, compared with Wistar rats. In GK rats, hexamethonium blocked i.c. RX77368-induced hypertensive and tachycardic responses, and reduced mortality by 86%, whereas phentolamine abolished the hypertensive response but enhanced tachycardia (+160 b.p.m.), and reduced mortality by 50%. The angiotensin II type 1 receptor antagonist irbesartan prevented i.c. RX77368-induced increases in blood pressure, HR and mortality. In conclusion, sympathetic overactivation triggered by brainstem TRH contributes to the mechanism of cardiovascular morbidity and mortality in T2D, which involves heightened cardiac inflammation and peripheral oxidative stress responses to sympathetic drive, and a mediating role of the renin-angiotensin system.

show abstract

Pathophysiology and Diagnosis of Disorders of the Adrenal Medulla: Focus on Pheochromocytoma

Lenders

Eisenhofer

2014

Comprehensive Physiology

View full text Add to dashboard Cite

The principal function of the adrenal medulla is the production and secretion of catecholamines. During stressful challenging conditions, catecholamines exert a pivotal homeostatic role. Although the main adrenomedullary catecholamine, epinephrine, has a wide array of adrenoreceptor-mediated effects, its absence does not cause life-threatening problems. In contrast, excess production of catecholamines due to an adrenomedullary tumor, specifically pheochromocytoma, results in significant morbidity and mortality. Despite being rare, pheochromocytoma has a notoriously bad reputation because of its potential devastating effects if undetected and untreated. The paroxysmal signs and symptoms and the risks of missing or delaying the diagnosis are well known for most physicians. Nevertheless, even today the diagnosis is still overlooked in a considerable number of patients. Prevention and complete cure are however possible by early diagnosis and appropriate treatment but these patients remain a challenge for physicians. Yet, biochemical proof of presence or absence of catecholamine excess has become more easy and straightforward due to developments in assay methodology. This also applies to radiological and functional imaging techniques for locating the tumor. The importance of genetic testing for underlying germline mutations in susceptibility genes for patients and relatives is increasingly recognized. Yet, the effectiveness of genetic testing, in terms of costs and benefits to health, has not been definitively established. Further improvement in knowledge of genotype-phenotype relationships in pheochromocytoma will open new avenues to a more rationalized and personalized diagnostic approach of affected patients.

show abstract

Sympathetic Nervous Activation in Essential Hypertension

Cited by 19 publications

References 16 publications

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Role of brainstem thyrotropin-releasing hormone-triggered sympathetic overactivation in cardiovascular mortality in type 2 diabetic Goto–Kakizaki rats

Pathophysiology and Diagnosis of Disorders of the Adrenal Medulla: Focus on Pheochromocytoma

Contact Info

Product

Resources

About