Protective effects of I(1)-antihypertensive agent moxonidine against neurogenic cardiac arrhythmias in halothane-anesthetized rabbits

J Pharmacol Exp Ther. 2000 Jun;293(3):929-38.

Abstract

Numerous studies have addressed the antihypertensive properties of I(1)-imidazoline receptor agonists such as moxonidine, but very few authors examined their cardiac antiarrhythmic potency. Due to the important role of the sympathetic nervous system in the genesis of neurogenic cardiac arrhythmias, we investigated the antiarrhythmic effects of moxonidine and compared them to those of propranolol in an experimental model of neurogenic arrhythmias. Chronic bipolar electrodes were implanted within the posterior hypothalamus of six halothane-anesthetized rabbits. Every 15 days, after three 10-min-interval control electrical stimulations, we compared the effects of randomized i.v. administrations of moxonidine (25 microg/kg), propranolol (0.5 mg/kg), and saline (0.9% NaCl) on mean arterial pressure (MAP), heart rate (HR), and ECG during 2.5 h with six stimulations every 20 min. We observed that: 1) in control conditions, intrahypothalamic stimulation increased MAP (DeltaMAP = 17 +/- 2 mm Hg) and HR (DeltaHR = 60 +/- 1 beats/min), and triggered extrasystoles (number of extrasystoles = 55 +/- 2) and abnormal complexes (number of abnormal ECG complexes = 37 +/- 1), which occurred with a 6.4 +/- 0.4-s delay and 33 +/- 1-s duration; 2) moxonidine and propranolol induced almost equihypotensive (DeltaMAP = -12 +/- 2 and -10 +/- 2 mm Hg) and pronounced bradycardic effects (DeltaHR = -47 +/- 10 and -78 +/- 9 beats/min, respectively). Arrhythmias were significantly reduced by moxonidine and propranolol: Deltanumber of extrasystoles = -83 and -98%; Deltanumber of abnormal ECG complexes = -33 and -79%; Deltadelay = +65 and +188%; Deltaduration = -35 and -58%, respectively. Our results show that moxonidine presents an antiarrhythmic potency comparable to that of propranolol that should be predominantly related to their central action. However, additional studies are required to determine whether these antiarrhythmic effects are of central and/or peripheral origin.

MeSH terms

  • Anesthesia
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Antihypertensive Agents / pharmacology*
  • Arrhythmias, Cardiac / prevention & control*
  • Blood Pressure / drug effects
  • Electrocardiography
  • Halothane / pharmacology*
  • Heart Rate / drug effects
  • Imidazoles / pharmacology*
  • Imidazoline Receptors
  • Male
  • Propranolol / pharmacology
  • Rabbits
  • Receptors, Drug / agonists*

Substances

  • Anti-Arrhythmia Agents
  • Antihypertensive Agents
  • Imidazoles
  • Imidazoline Receptors
  • Receptors, Drug
  • Propranolol
  • moxonidine
  • Halothane