Cardiac electrophysiological effects of selective adrenoceptor stimulation and their possible roles in arrhythmias.
The selective alpha 1- and alpha 2-adrenoceptor agonists St 587 and BHT 933, respectively, and the antagonists prazosin (alpha 1) and WY 25309 (alpha 2) have been used in combination with the selective beta 2-adrenoceptor agonist pirbuterol, and the antagonists atenolol (beta 1) and ICI 118551 (beta 2), to analyse the effects of individual types of adrenoceptor stimulation in various parts of the rabbit heart. In the sinus node, beta 1-, but not beta 2-adrenoceptor stimulation increased the fast phase of depolarisation. Both beta 1- and beta 2-adrenoceptor stimulation increased the slope of the slow diastolic depolarisation, accelerated repolarisation, and increased maximum diastolic potential. Beta 1- and beta 2-adrenoceptor stimulation also accelerated repolarisation in Purkinje cells and papillary muscle. After blockade of both beta 1- and beta 2-adrenoceptors, alpha 1-adrenoceptor stimulation caused bradycardia, owing exclusively to delayed repolarisation. Alpha 2-adrenoceptor stimulation had no effect. Beta 1-, but not beta 2-adrenoceptor stimulation augmented peak contractions three- to fivefold, and reduced the time-to-peak tension. In contrast, alpha 1-adrenoceptor stimulation only moderately (up to 47%) increased peak tension, but increased time-to-peak and duration of contractions. The results would be consistent with beta 1-adrenoceptor stimulation increasing inward calcium current, and with stimulation of alpha 1-adrenoceptors delaying the decline of [Ca]i rather than increasing its magnitude. Both beta 1- and beta 2-stimulation increased repolarising current, but alpha 1-stimulation decreased it.
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Vaughan Williams
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000032:analysis / Q000502:physiology*
D011941:Receptors, Adrenergic; D010656:Phenylephrine; D007545:Isoproterenol; D011224:Prazosin