Effects of selective alpha 1-, alpha 2-, beta 1-and beta 2-adrenoceptor stimulation on potentials and contractions in the rabbit heart

J Physiol. 1984 Oct:355:523-46. doi: 10.1113/jphysiol.1984.sp015436.

Abstract

Selective adrenoceptor agonists and antagonists have been used to analyse the effects of stimulation of individual types of adrenoceptor in various parts of the rabbit heart. The selective alpha 1- and alpha 2-adrenoceptor agonists used were St 587 and BHT 933 respectively, and the antagonists were prazosin (alpha 1) and WY 25309 (alpha 2). The selective beta 1- and beta 2-adrenoceptor antagonists were atenolol and ICI 118551, respectively. Pirbuterol was a highly selective beta 2-adrenoceptor agonist. The non-selective agonists noradrenaline, adrenaline and isoprenaline were also employed with various combinations of antagonists. Phenylephrine was found to stimulate beta- as well as alpha-adrenoceptors. Rimiterol was a beta-adrenoceptor agonist, partially selective for beta 2-adrenoceptors. In the sinus node beta 1-, but not beta 2-adrenoceptor stimulation increased the fast phase of depolarization (Vmax). Both beta 1- and beta 2-adrenoceptor stimulation increased the slope of slow diastolic depolarization, accelerated repolarization and increased maximum diastolic potential. After blockade of both beta 1- and beta 2-adrenoceptors alpha 1-adrenoceptor stimulation caused bradycardia, due exclusively to delayed repolarization. alpha 2-adrenoceptor stimulation had no effect. In Purkinje cells and papillary muscle both beta 1- and beta 2-adrenoceptor stimulation accelerated repolarization. Stimulation of alpha 2-adrenoceptors had no effect. Beta 1-, not beta 2-adrenoceptor stimulation augmented peak contractions 3-5-fold, and greatly increased rate of development of tension. After beta-blockade alpha 1-adrenoceptor stimulation moderately increased peak contractions (up to 47%), but increased time-to-peak and duration of contractions. These patterns of adrenoceptor-mediated effects were unchanged in animals pre-treated with sufficient 6-hydroxydopamine to eliminate responses to sympathetic nerve stimulation. The results would be consistent with beta 1-, and beta 2-adrenoceptor stimulation increasing inward calcium current, and with stimulation of alpha 1-adrenoceptors delaying its inactivation, rather than increasing its magnitude.

MeSH terms

  • Action Potentials / drug effects
  • Adrenergic Agonists / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Heart / drug effects
  • Heart / physiology*
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Myocardial Contraction / drug effects*
  • Papillary Muscles / drug effects
  • Purkinje Cells / drug effects
  • Rabbits
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, beta / drug effects
  • Sinoatrial Node / drug effects
  • Sympatholytics / pharmacology*

Substances

  • Adrenergic Agonists
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Sympatholytics