title: Effects of selective alpha 1-, alpha 2-, beta 1-and beta 2-adrenoceptor stimulation on potentials and contractions in the rabbit heart.
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: D000200:Action Potentials / Q000187:drug effects; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology*
chemical_list: D000322:Adrenergic Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013565:Sympatholytics