The sympathetic nervous system alterations in human hypertension

Abstract

Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

Keywords: hypertension essential; renal insufficiency; sympathetic nervous system.

© 2015 American Heart Association, Inc.

Figures

Figure 1

Relationships between heart rate (HR) and muscle sympathetic nerve traffic (MSNA), as assessed by the microneurographic technique in the peroneal nerve (MSNA, expressed as bursts frequency over time), in healthy controls, essential hypertensive patients, obese subjects and patients with heart failure. In each panel number of subjects (n), correlation coefficients (r) and P values are shown. Note that only in heart failure patients a significant relationship was found. Figure redrawn from data of Ref .

Figure 2

Summary of differences in sympathetic activity in obese and lean normotensive and hypertensive subjects. NE: norepinephrine, MSNA: muscle sympathetic nerve activity.

Figure 3

Schematic diagram depicting the balance between the sympathetic and vasodilator actions of insulin in the regulation of blood pressure normal humans (left panel) and the potential effect on blood pressure of potentiated sympathetic action and/or attenuated vasodilator action of insulin in obesity and hypertension (right panel).

Figure 4

Measurements of renal norepinephrine spillover to plasma, used to assess sympathetic activity in the kidneys in healthy volunteers and patients with arterial hypertension. Renal sympathetic activation was commonly evident in hypertensive patients. In untreated patients with mild-moderately severe essential hypertension (middle column), renal norepinephrine spillover was increased overall, and elevated in approximately 50%. In drug-resistant hypertension, with patients administered on average five antihypertensive drug classes, renal norepinephrine spillover was higher again, attributable to their hypertension, and perhaps its treatment. From unpublished data by Murray Esler, Markus Schlaich, Gavin Lambert and Dagmara Hering.

Figure 5

Regional norepinephrine spillover to plasma is a validated test for sympathetic denervation, being used in the diagnosis of patients with pure autonomic failure who have sympathetic denervation due to disease. Testing was done before and 30 days after the procedure. SYMPLICITY Arch and Flex catheters were used in approximately equal numbers, with similar results. The renal sympathetic denervation was incomplete, sometimes markedly so, with pronounced non-uniformity between individual patients, contradicting the idea that achieving sympathetic denervation is technically “easy”. Blood pressure non-response to renal denervation must commonly be due to suboptimal denervation, not only to the absence of sympathetic nervous activation in individual patients, often invoked as the determinant of non-responder status. From unpublished data by Murray Esler, Markus Schlaich, Gavin Lambert and Dagmara Hering.