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

Circulation. 2004 Nov 2;110(18):2786-91. doi: 10.1161/01.CIR.0000146335.69413.F9. Epub 2004 Oct 25.

Abstract

Background: The possible mechanisms by which beta-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 beta-blockade associated with unchanged values of arterial blood pressure and baroreflex sensitivity. We tested the hypothesis that acute beta-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 (alpha-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, alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Atenolol / administration & dosage
  • Atenolol / pharmacology*
  • Baroreflex / drug effects
  • Blood Pressure / drug effects
  • Electrocardiography
  • Epinephrine / blood
  • Female
  • Heart Rate / drug effects
  • Humans
  • Injections, Intravenous
  • Male
  • Muscle, Skeletal / innervation*
  • Norepinephrine / blood
  • Peroneal Nerve / drug effects*
  • Peroneal Nerve / physiology
  • Respiration / drug effects
  • Sympathetic Fibers, Postganglionic / drug effects*
  • Sympathetic Fibers, Postganglionic / physiology
  • Vasoconstriction / drug effects
  • Vasomotor System / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Atenolol
  • Norepinephrine
  • Epinephrine