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Sympathetic Mechanism of Hypertension
Sympathetic Mechanism of Hypertension
191
Sympathetic Mechanism of Hypertension Italo Biaggioni Vanderbilt University School of Medicine, USA
The autonomic nervous system is not only crucial role in the instantaneous regulation of blood pressure, but also contributes to the chronic maintenance of hypertension, as evidenced by conditions resulting from lesions of autonomic pathways and recent findings in obesity- and resistanthypertension. Lesions of baroreflex pathways in the neck (following surgery or radiation) or the NTS, lead to labile hypertension. Neurovascular compression of the RVLM is associated with hypertension. Neurodegeneration of central autonomic pathways (multiple system atrophy) is accompanied by severe supine hypertension driven by residual sympathetic tone. These rare disorders support the concept that abnormal autonomic mechanisms can contribute to the maintenance of hypertension. Obesity, the most common cause of hypertension, is characterized by selective activation of sympathetic pathways involved in cardiovascular regulation. Furthermore, blood pressure is virtually normalized in animal models of obesity hypertension with chronic carotid sinus stimulation and in patients by autonomic withdrawal with ganglionic blockade. It was thought that sympathetic activity is increase in obesity as a compensatory mechanism to increase energy expenditure. However, clinical studies have shown that blood pressure is virtually normalized by ganglionic blockade in obese hypertensives, but the elevated resting energy expenditure associated with obesity is not. Furthermore, sympathetic activation may contribute to insulin resistance. Sympathetic activation was one of the first targets in the treatment of hypertension, but current antihypertensives aiming the autonomic nervous system are limited by side effects. This void is being filled by interventional approaches such electrical stimulation of the carotid sinus, and catheter ablation of renal afferent nerves. These novel devices are currently being tested for the treatment of resistant hypertension.
References 1. Shibao C, Gamboa A, Diedrich A, Ertl AC, Chen KY, Byrne DW, et al. Autonomic contribution to blood pressure and metabolism in obesity. HTN. 2007;49(1):27 33. 2. Esler MD, Eikelis N, Lambert E, Straznicky N. Neural mechanisms and management of obesity-related hypertension. CurrCardiolRep. 2008;10(6):456 63. 3. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010 Dec 4;376(9756):1903 9. 4. Lohmeier TE, Iliescu R, Liu B, Henegar JR, Maric-Bilkan C, Irwin ED. Systemic and renal-specific sympathoinhibition in obesity hypertension. Hypertension. 2012 Feb;59(2):331 8. 5. Biaggioni I. Interventional approaches to reduce sympathetic activity in resistant hypertension: to ablate or stimulate? HTN. 2012 Feb;59(2):194 5.
191
Sympathetic Mechanism of Hypertension Italo Biaggioni Vanderbilt University School of Medicine, USA
The autonomic nervous system is not only crucial role in the instantaneous regulation of blood pressure, but also contributes to the chronic maintenance of hypertension, as evidenced by conditions resulting from lesions of autonomic pathways and recent findings in obesity- and resistanthypertension. Lesions of baroreflex pathways in the neck (following surgery or radiation) or the NTS, lead to labile hypertension. Neurovascular compression of the RVLM is associated with hypertension. Neurodegeneration of central autonomic pathways (multiple system atrophy) is accompanied by severe supine hypertension driven by residual sympathetic tone. These rare disorders support the concept that abnormal autonomic mechanisms can contribute to the maintenance of hypertension. Obesity, the most common cause of hypertension, is characterized by selective activation of sympathetic pathways involved in cardiovascular regulation. Furthermore, blood pressure is virtually normalized in animal models of obesity hypertension with chronic carotid sinus stimulation and in patients by autonomic withdrawal with ganglionic blockade. It was thought that sympathetic activity is increase in obesity as a compensatory mechanism to increase energy expenditure. However, clinical studies have shown that blood pressure is virtually normalized by ganglionic blockade in obese hypertensives, but the elevated resting energy expenditure associated with obesity is not. Furthermore, sympathetic activation may contribute to insulin resistance. Sympathetic activation was one of the first targets in the treatment of hypertension, but current antihypertensives aiming the autonomic nervous system are limited by side effects. This void is being filled by interventional approaches such electrical stimulation of the carotid sinus, and catheter ablation of renal afferent nerves. These novel devices are currently being tested for the treatment of resistant hypertension.
References 1. Shibao C, Gamboa A, Diedrich A, Ertl AC, Chen KY, Byrne DW, et al. Autonomic contribution to blood pressure and metabolism in obesity. HTN. 2007;49(1):27 33. 2. Esler MD, Eikelis N, Lambert E, Straznicky N. Neural mechanisms and management of obesity-related hypertension. CurrCardiolRep. 2008;10(6):456 63. 3. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010 Dec 4;376(9756):1903 9. 4. Lohmeier TE, Iliescu R, Liu B, Henegar JR, Maric-Bilkan C, Irwin ED. Systemic and renal-specific sympathoinhibition in obesity hypertension. Hypertension. 2012 Feb;59(2):331 8. 5. Biaggioni I. Interventional approaches to reduce sympathetic activity in resistant hypertension: to ablate or stimulate? HTN. 2012 Feb;59(2):194 5.