Cardiovascular Effects of Clenbuterol Are Beta 2-adrenoceptor-mediated in Steers

J Anim Sci. 1995 Jun;73(6):1754-65. doi: 10.2527/1995.7361754x.

Abstract

The mechanism through which the repartitioning agent clenbuterol increases heart rate was investigated. First, the relative importance of the beta 1- and beta 2-adrenoceptors was established in rat and bovine right atria in vitro. The positive chronotropic and inotropic effects of (+/-)isoproterenol in rat and bovine right atria, respectively, were markedly antagonized (P < .001) by the beta 1-adrenoceptor antagonist CGP 20712A but were antagonized less by the beta 2-adrenoceptor antagonist ICI 118 551 in rat (P < .01), but not in bovine atria, indicating a major role of the beta 1-adrenoceptors. Clenbuterol was only a partial agonist in rat right atria, increasing heart rate at high concentrations through stimulation of beta 1-adrenoceptors. In studies in vivo, clenbuterol decreased the plasma potassium concentration (P < .05) and increased the plasma glucose concentration (P < .05). Clenbuterol also reduced diastolic blood pressure (P < .01) and increased heart rate (P < .001). The increase in heart rate was not due to direct stimulation of cardiac beta 1-adrenoceptors by clenbuterol but was consistent with a reflex response to beta 2-adrenoceptor-mediated hypotension. This would have caused the activation of baroreceptors, which in turn would have resulted in both the release of norepinephrine to stimulate cardiac beta 1-adrenoceptors and the inhibition of cholinergic input to the heart. Thus, the effects of clenbuterol could be eliminated completely by ICI 118 551 or reduced by approximately 50% using CGP 20712A. The combination of treatment of clenbuterol and CGP 20712A could be useful. It may allow the full repartitioning effects seen with the beta 2-agonist alone, but with a markedly attenuated effect on the heart. Such a treatment regimen may also help reduce the increased energy expenditure and loss of appetite seen following the initial administration of clenbuterol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Atrial Function
  • Blood Glucose / analysis
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cardiovascular Physiological Phenomena
  • Cardiovascular System / drug effects*
  • Cattle / physiology*
  • Clenbuterol / administration & dosage
  • Clenbuterol / pharmacology*
  • Dose-Response Relationship, Drug
  • Heart Atria / chemistry
  • Heart Atria / ultrastructure
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Imidazoles / pharmacology
  • Infusions, Intravenous
  • Isoproterenol / pharmacology
  • Male
  • Norepinephrine / pharmacology
  • Potassium / blood
  • Propanolamines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-1 / analysis
  • Receptors, Adrenergic, beta-1 / physiology
  • Receptors, Adrenergic, beta-2 / analysis
  • Receptors, Adrenergic, beta-2 / physiology*

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Antagonists
  • Blood Glucose
  • Imidazoles
  • Propanolamines
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • ICI 118551
  • CGP 20712A
  • Isoproterenol
  • Potassium
  • Norepinephrine
  • Clenbuterol