Effects of alpha-adrenergic agents on generation of oscillatory afterpotentials and triggered activity in rabbit Purkinje fibers.
Effects of alpha 1- and alpha 2-adrenergic agonists and antagonists on oscillatory afterpotentials (OAP) and triggered activity induced by acetylstrophanthidin (AS) or 8 mM Ca2+ (with 2 mM K+) were studied with standard microelectrode techniques in isolated rabbit heart Purkinje fibers. Experiments were conducted in the presence of 0.5 microM propranolol. Phenylephrine (PE, 0.5 to 10 microM) increased the amplitude of OAP and induced triggered activity when subthreshold OAP were caused by high Ca2+. In contrast, PE decreased the amplitude of OAP and suppressed triggered activity induced by acetylstrophanthidin. Prazosin at 0.5 microM did not affect the amplitudes of OAP by itself, but abolished both the inhibitory effect of PE on AS-induced OAP and the stimulatory effect of PE on high Ca2(+)-induced OAP. At 2 microM, prazosin alone reduced the amplitude of OAP and suppressed triggered activity induced by either acetylstrophanthidin or high Ca2+. While clonidine (0.5 to 10 microM) did not affect OAP or induction of triggered activity, yohimbine (2 microM) decreased the amplitude of OAP and abolished triggered activity induced by either acetylstrophanthidin or high Ca2+. Thus, specific alpha 1-adrenergic actions of phenylephrine may exert either pro-arrhythmic or antiarrhythmic effects on OAP and triggered activity depending on the method of induction of OAP. The alpha 1- and alpha 2-antagonists prazosin and yohimbine both exert direct antiarrhythmic effects in addition to their adrenergic blocking actions.
Han
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Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ferrier
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D013327:Strophanthidin; D011433:Propranolol; C004681:acetylstrophanthidin; D003000:Clonidine; D011188:Potassium; D002118:Calcium; D011224:Prazosin