Termination of digitalis-induced ventricular tachycardias by clonidine involves central alpha 2-adrenoceptors in cats

Br J Pharmacol. 1991 May;103(1):1114-8. doi: 10.1111/j.1476-5381.1991.tb12309.x.

Abstract

1. Effects of intravenous (i.v.) and intravertebral arterial (i.a.) administration of the alpha 2-adrenoceptor agonist, clonidine (Clon) and its antagonist, yohimbine (Yoh, 0.5 mg kg-1, i.v.; 0.05 mg kg-1, i.a.), on ventricular tachycardia (VT) induced by intravenous acetylstrophanthidin (AS) were studied in cats anaesthetized with intraperitoneal chloralose. 2. AS dose-dependently produced cardiac arrhythmias including complete atrioventricular conduction block (118 +/- 14 micrograms kg-1, i.v.), junctional tachycardia (128 +/- 20 micrograms kg-1, i.v.), multiform ventricular premature beats (157 +/- 21 micrograms kg-1, i.v.) and sustained VT (220 +/- 23 micrograms kg-1, i.v.). 3. Doses of Clon (i.v.) required for termination of VT following i.v. Yoh (62.9 +/- 5.2 micrograms kg-1) or i.a. Yoh (88.5 +/- 16.3 micrograms kg-1) were higher than those for termination of VT without Yoh administration (28.3 +/- 6.2 micrograms kg-1). Doses of Clon (i.a.) required for termination of VT without or with i.a. Yoh administration were 5.8 +/- 1.0 or 14.8 +/- 3.7 micrograms kg-1, respectively, and they were significantly different. 4. These experiments demonstrate that either i.v. or i.a. Yoh antagonizes the antiarrhythmic effect of Clon on AS-induced VT. Since small doses of Clon administered i.a. act predominantly on the central nervous system, we suggest that its antiarrhythmic effect is likely to be on central alpha 2-adrenoceptors in the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents
  • Blood Pressure / drug effects
  • Cats
  • Clonidine / pharmacology*
  • Digitalis Glycosides / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Electrophysiology
  • Female
  • Male
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology*
  • Strophanthidin / analogs & derivatives
  • Strophanthidin / pharmacology
  • Tachycardia / chemically induced
  • Tachycardia / drug therapy*
  • Yohimbine / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Digitalis Glycosides
  • Receptors, Adrenergic, alpha
  • Yohimbine
  • Strophanthidin
  • acetylstrophanthidin
  • Clonidine