Acute β-Blockade Increases Muscle Sympathetic Activity and Modifies Its Frequency Distribution

Abstract

Background— The possible mechanisms by which β-adrenergic antagonists may act on the neural regulation of the cardiovascular system are still elusive. Recent studies reported a marked increase of postganglionic muscle sympathetic nerve activity (MSNA) after acute β-blockade associated with unchanged values of arterial blood pressure and baroreflex sensitivity. We tested the hypothesis that acute β-blockade might also alter the oscillatory characteristics of MSNA, thus decreasing its effectiveness on peripheral vasoconstriction. Methods and Results— In 11 healthy volunteers, ECG, MSNA, arterial pressure, and respiration were recorded before and after atenolol (0.05 mg/kg IV bolus) administration. The frequency distribution of RR interval, MSNA, systolic arterial pressure (SAP), and respiratory variability was assessed by spectrum and cross-spectrum analysis. Spontaneous baroreflex sensitivity (α-index) and plasma catecholamines (high-performance liquid chromatography) were measured. Atenolol induced a significant increase in RR interval (14.3±1.6%) with no changes in systolic and diastolic arterial pressure. MSNA increased (42±13% from 18±2 bursts per minute). The low-frequency (LF) component of RR and MSNA variability decreased (−44±7% and −24±5%, respectively), whereas the high-frequency (HF) component increased (163±55% and 34±11%, respectively), expressed in normalized units. Spectral coherence, an index of oscillatory coupling, decreased between LF RR and LF MSNA , whereas it increased between HF MSNA and HF Resp . SAP variability, α-index, and plasma catecholamines remained unchanged. Conclusions— Atenolol induced a change in MSNA frequency distribution reflecting a stronger respiratory coupling. This shift toward high frequency, despite an increase in MSNA, may lead to a less efficient sympathetic vasomotor modulation.