Contrasting preganglionic and postganglionic effects of phenylephrine on parasympathetic control of heart rate.
Previous reports indicate that alpha-adrenergic agonists modulate vagal control of heart rate. In the rat, phenylephrine inhibition of vagal-stimulated bradycardia may be occurring at any of a number of sites along the cardiac parasympathetic pathway. The purpose of the present experiments was to localize the pre- or postganglionic sites of phenylephrine modulation of parasympathetic-mediated bradycardia in the rat. Sprague-Dawley rats were anesthetized and instrumented with arterial and venous catheters and electrocardiographic leads. The cervical vagi were sectioned, and propranolol was administered. The right cervical vagus nerve was electrically stimulated to activate preganglionic parasympathetic nerves. Carbachol was injected to activate nicotinic receptors on postganglionic parasympathetic nerves (i.e., intracardiac ganglion cells). Methacholine was injected to activate muscarinic receptors at the sinoatrial node. The heart rate responses to these three interventions were recorded before, during, and after phenylephrine infusion. Phenylephrine significantly attenuated the bradycardia produced by vagal nerve stimulation. In contrast, phenylephrine facilitated the bradycardia elicited by carbachol injection. Since carbachol has both muscarinic and nicotinic effects, the results were compared with those obtained from methacholine, a pure muscarinic agonist. Phenylephrine had no effect on methacholine-induced bradycardia, suggesting that the modulation of the carbachol response was through carbachol's nicotinic effects. Yohimbine, the alpha 2-receptor antagonist, eliminated phenylephrine-mediated facilitation of the carbachol response. These data indicate that phenylephrine has contrasting effects on pre- and postganglionic cardiac parasympathetic nerves in rats: inhibition at preganglionic sites (vagal stimulation results) and facilitation at the level of the ganglion cells (carbachol experiments).
Pardini
B J
BJ
Veterans Affairs Medical Center, Iowa City, Iowa.
Lund
D D
DD
Schmid
P G
PG
D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology*; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D010656:Phenylephrine; D015016:Yohimbine; D002217:Carbachol; D011433:Propranolol