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

• Published in: The Journal of physiology Vol. 355; no. 1; pp. 523 - 546
• Main Authors: Dukes, I D, Vaughan Williams, E M
• Format: Journal Article
• Language: English
• Published: England The Physiological Society 01-10-1984
• Subjects: 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
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1984.sp015436

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.