Sympathetic Responses to Antihypertensive Treatment Strategies : Implications for the Residual Cardiovascular Risk

Abstract

Purpose of Review: To examine whether and to what extent lifestyle, pharmacological and device-based therapeutic blood pressure lowering interventions are capable to restore a normal sympathetic cardiovascular function in hypertensive patients.

Recent Findings: Data collected by examining the results of more than 50 studies published during the past years by directly quantifying, via microneurography, the sympathetic nerve traffic responses to non-pharmacological and pharmacological antihypertensive treatment have shown that no normalization of the sympathetic cardiovascular function is achieved. Recently, a study by our group carried out in 219 hypertensive patients under monotherapy or combination drug treatment confirmed these results, by showing that, despite achieving an optimal blood pressure control, antihypertensive treatment fails to restore the normal sympathetic neural function detected in the normotensive healthy subjects.

Summary: The sympathetic nervous system plays a key role in blood pressure regulation and hypertension pathophysiology. Recent findings document its involvement also in determining the blood pressure lowering effects of antihypertensive agents. However, the available data show the inability to achieve during treatment a full sympathetic normalization, a finding which may represent one of the mechanisms responsible for the residual cardiovascular risk of the treated hypertensive patient.

Keywords: Antihypertensive drug treatment; Carotid baroreceptor stimulation; Lifestyle interventions; Muscle sympathetic nerve traffic; Renal denervation; Residual cardiovascular risk; Sympathetic activity.

Fig. 1

Effects of lifestyle interventions (physical exercise training and low caloric diet program) on systolic (S) and diastolic (D) blood pressure (BP, left panel) and muscle sympathetic nerve traffic (MSNA, right panel) in essential hypertensive patients enrolled in different microneurographic studies [–22]. Black columns refer to values recorded under baseline condition pre-lifestyle intervention, while grey columns to values recorded at the end of the lifestyle intervention period. A group of age-matched normotensive subjects (NTs) is shown for comparison. Numbers of subjects included in each group are shown in parentheses. Data are shown as means ± standard deviations (SD). Asterisks (P < 0.01) refer to the level of statistical significance between values recorded before and at the end of the lifestyle intervention program. The symbol ‡ (P < 0.01) refers to the level of statistical significance between values recorded in hypertensive patients at the end of the lifestyle intervention program and values recorded in pure normotensive controls

Fig. 2

Effects of antihypertensive single drug treatment on systolic (S) and diastolic (D) blood pressure (BP, left panel) and muscle sympathetic nerve traffic (MSNA, right panel) in essential hypertensive patients enrolled in different microneurographic studies [–43]. Black columns refer to values recorded under baseline no-drug condition (Baseline), while grey columns to values recorded under single drug (Mono) treatment. A group of age-matched normotensive subjects (NTs) is shown for comparison. Asterisks (**P < 0.01) refer to the level of statistical significance between values recorded in the no-drug condition and during treatment. The symbol ‡ (P < 0.01) refers to the level of statistical significance between values recorded in treated hypertensive patients and values recorded in pure normotensive controls. For other symbols and abbreviations see preceding figure

Fig. 3

Effects of antihypertensive combination drug treatment on systolic (S) and diastolic (D) blood pressure (BP, left panel) and muscle sympathetic nerve traffic (MSNA, right panel) in essential hypertensive patients enrolled in different microneurographic studies [, –48]. Black columns refer to values recorded under baseline no-drug condition (Baseline), while grey columns to values recorded under combination drug (Combo) treatment. For other explanations and symbols see legend Fig. 2

Fig. 4

Effects of bilateral renal nerves ablation (RDN) and carotid baroreceptor activation therapy (BAT) on systolic (S) and diastolic (D) blood pressure (BP, left panel) and muscle sympathetic nerve traffic (MSNA, right panel) in resistant hypertensive patients enrolled in different microneurographic studies [–59]. Black columns refer to values recorded under baseline condition, while grey columns to values recorded under RDN and BAT. Asterisks (*P < 0.05, **P < 0.01) refer to the level of statistical significance between values recorded before and after BAT and RDN. For other symbols and explanations see legends of the preceding figures

Fig. 5

Systolic (S) and diastolic (D) blood pressure (BP, left panel) and muscle sympathetic nerve traffic (MSNA, right panel) in untreated hypertensive patients (U), treated hypertensives with controlled (C) and tightly controlled (TC) BP values. A group of age-matched normotensive subjects (NTs) is shown for comparison. Asterisks (*P < 0.05, **P < 0.01) refer to the level of statistical significance between groups. Data from Ref 67