Refractory period response of cardiac Purkinje tissue to alpha 1- and alpha 2-adrenergic influences.
Our purpose was to characterize Purkinje responses in vivo to alpha 1- and alpha 2-adrenergic stimulation in sinoaortically denervated and vagotomized dogs pretreated with metoprolol (1 mg/kg). We measured Purkinje relative refractory period (PRRP) responses to norepinephrine (NE) and phenylephrine (PE) with prazosin and/or yohimbine, WB-4101, and chloralethylclonidine (CEC) in varying doses. Results were as follows: PE infusion (25 micrograms.kg-1.min-1) prolonged PRRP (9.6 +/- 1.4 ms; a 4.1 +/- 0.4% change). Prazosin blocked PRRP prolongation with PE at 7 x 10(-8) M/kg (P < 0.05). Yohimbine did not attenuate PRRP prolongation with PE either alone or in combination with prazosin. NE infusion (0.8 micrograms.kg-1.min-1) also prolonged PRRP (9.2 +/- 2.3 ms; a 4.8 +/- 1.0% change). In contrast neither prazosin nor yohimbine at any dose (up to 10(-6) M/kg) totally blocked the prolongation with NE infusion. However, with prazosin (2 x 10(-7) M/kg) pretreatment, yohimbine blocked PRRP prolongation, significant at 7 x 10(-8) M/kg (P < 0.05). In separate experiments with yohimbine pretreatment at 7 x 10(-8) M/kg, PRRP prolongation with either PE or NE infusion was blocked equipotently with WB-4101 and CEC at 7 x 10(-8) M/kg. However, CEC did not block mean arterial pressure (MAP) responses to PE or NE infusion unlike WB-4101. We concluded that both subclasses of alpha 1-adrenergic antagonists equipotently block PRRP prolongation by alpha-agonists despite different effects on MAP. Purkinje refractoriness is also prolonged by alpha 2-adrenergic stimulation acting at the cell membrane.
Cable
D G
DG
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Rath
T E
TE
Dreyer
E R
ER
Martins
J B
JB
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012032:Refractory Period, Electrophysiological
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D009638:Norepinephrine