Acute β-blockade increases muscle sympathetic activity and modifies its frequency distribution

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.