title: Presynaptic effect of muscle relaxants on the release of 3H-norepinephrine controlled by endogenous acetylcholine in guinea pig atrium.
abstract: The influence of nondepolarizing muscle relaxants (MR) on the resting and electrically evoked release of tritiated norepinephrine (3H-NE) was investigated, in the absence and presence of 10(-4) mol/l cocaine, in the in vitro right atrium preparation of guinea pigs (g.p.) preloaded with 3H-NE. In the absence of MR both resting and stimulated 3H and 3H-NE release remained relatively constant throughout the experiment and the ratios of the evoked release of 3H during consecutive stimulation periods (i.e. S2/S1, S3/S2) were close to unity. None of the MR had any effect on resting 3H release. Atropine (3 x 10(-7) mol/l), gallamine (7 x 10(-5) mol/l), and pancuronium (2 x 10(-6) mol/l), but not d-tubocurarine (5 x 10(-6) mol/l) significantly increased stimulated release of 3H-NE. The effect of MR on resting or evoked release of 3H-NE was not influenced by 10(-4) mol/l cocaine. In the presence of atropine gallamine and pancuronium did not affect the release of 3H-NE. This finding indicates that the effect of MR was mediated via presynaptic muscarinic receptors. Muscle relaxants and atropine inhibited these receptors and removed the tonic inhibitory effect of acetylcholine (ACh) released from the parasympathetic nerve endings on the release of NE from the sympathetic nerve. This was substantiated by the finding that in the present of cholinesterase inhibition, when the effect of endogenous ACh was amplified and thereby the cholinergic tone was dominant, the total release of 3H-NE evoked by stimulation was much lower and muscle relaxants and atropine were much more effective to enhance 3H-NE release. Gallamine and pancuronium also increased the force of contraction of the electrically stimulated atria. These findings indicate that the acceleration of the heart rate observed with gallamine and pancuronium in anesthetized man is due to increased release from, and not the inhibition of reuptake of NE by the sympathetic nerve endings of the right atrium.
authors.affiliation: Department of Anesthesiology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: F F
authors.initials: FF
authors.lastname: Földes
authors.forename: O
authors.initials: O
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Kinjo
authors.forename: L G
authors.initials: LG
authors.lastname: Harsing
authors.forename: H
authors.initials: H
authors.lastname: Nagashima
authors.forename: D
authors.initials: D
authors.lastname: Duncalf
authors.forename: P L
authors.initials: PL
authors.lastname: Goldiner
authors.forename: E S
authors.initials: ES
authors.lastname: Vizi
mesh_terms: D000109:Acetylcholine / Q000493:pharmacokinetics; D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000294:innervation*; D066298:In Vitro Techniques; D008297:Male; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000493:pharmacokinetics
chemical_list: D003473:Neuromuscular Nondepolarizing Agents; D001285:Atropine; D003042:Cocaine; D000109:Acetylcholine; D009638:Norepinephrine