Paradoxical inotropic effects of clonidine and labetalol in the conscious rabbit

J Cardiovasc Pharmacol. Jul-Aug 1981;3(4):818-27. doi: 10.1097/00005344-198107000-00015.

Abstract

Both clonidine and labetalol when given by bolus intravenous injection into conscious rabbits produce an initial rise in left ventricular pressure associated with a decrease in myocardial contractility as assessed by left ventricular dP/dt. While clonidine also produces a marked bradycardiac effect, labetalol causes no change in heart rate. Acute beta-adrenoceptor blockade with propranolol, 1 mg/kg, i.v., does not significantly modify the response produced by either clonidine or labetalol. Following cardiac cholinergic blockade with scopolamine methylbromide, 50 microgram/kg, the negative inotropic effect produced by clonidine is abolished and is replaced by a positive inotropic effect, while the negative inotropic response produced by labetalol is attenuated. Following cardiac autonomic blockade with propranolol and scopolamine methyl-bromide, both clonidine and labetalol produce a positive inotropic response. These positive inotropic responses may be due to the partial alpha-adrenoceptor-agonist properties which both drugs possess and which could be unmasked by cardiac autonomic blockade.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Clonidine / pharmacology*
  • Ethanolamines / pharmacology*
  • Heart Rate / drug effects
  • Labetalol / pharmacology*
  • Myocardial Contraction / drug effects*
  • Propranolol / pharmacology
  • Rabbits
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, beta / drug effects
  • Scopolamine / pharmacology
  • Stimulation, Chemical

Substances

  • Ethanolamines
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Propranolol
  • Scopolamine
  • Clonidine
  • Labetalol