Effects of five different airway smooth muscle relaxants on inhibitory neurotransmission in isolated guinea-pig trachea in vitro

Current asthma treatments using anti-inflammatory agents and airway smooth muscle (ASM) relaxants are expensive, variable in effectiveness and are associated with several cardiovascular side effects. Previous in vitro experiments conducted on ASM tissues suggest that oscillations applied to contracted muscle result in a reduction in the contractile ability of the tissue. This study focuses on investigating the combined effects of muscle relaxants (bronchodilators) and length oscillations on the dynamics of contracted ASM. Isolated porcine tracheal smooth muscle tissues are contracted using Acetylcholine. Isoproterenol (Iso), a β-agonist, is used as a bronchodilator to relax the contracted ASM. Our results suggest that the combined effect of Iso and breathing oscillations is noted to be greater than the added effects of Iso and breathing alone. It can be proposed that breathing oscillations aid the relaxation of ASM by Isoproterenol.

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The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

Brazilian Journal of Medical and Biological Research ◽

10.1590/s0100-879x1998000600014 ◽

1998 ◽

Vol 31 (6) ◽

pp. 811-818

Author(s):

A.C. Perez ◽

W. Paul ◽

S. Harrison ◽

C.P. Page ◽

D. Spina

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Airway Smooth Muscle ◽

Muscle Function ◽

Smooth Muscle Function

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Rapacuronium Preferentially Antagonizes the Function of M2 versus M3 Muscarinic Receptors in Guinea Pig Airway Smooth Muscle

Anesthesiology ◽

10.1097/00000542-200501000-00020 ◽

2005 ◽

Vol 102 (1) ◽

pp. 117-124 ◽

Cited By ~ 39

Author(s):

Edmund Jooste ◽

Yi Zhang ◽

Charles W. Emala

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Muscle Contraction ◽

Muscarinic Receptor ◽

Airway Smooth Muscle ◽

Muscarinic Receptors ◽

Muscle Tension ◽

Electrical Field Stimulation ◽

Muscle Relaxants ◽

Parasympathetic Nerves

Background Rapacuronium, a nondepolarizing muscle relaxant that was proposed as a replacement for succinylcholine for rapid intubation, was withdrawn from clinical use as a result of fatal bronchospasm, but the mechanism of this effect is not known. Preferential antagonism of presynaptic M2 muscarinic receptors versus postsynpatic M3 muscarinic receptors can facilitate bronchoconstriction. The authors questioned whether rapacuronium preferentially antagonized M2 versus M3 muscarinic receptors in intact airway. Methods Guinea pig tracheal rings were suspended in organ baths and muscle relaxants' antagonism of prejunctional M2 muscarinic autoreceptors was evaluated by augmentation of muscle contraction elicited by electrical field stimulation. Muscle relaxants' antagonism of postjunctional M3 muscarinic receptors was assessed by attenuation of muscle contraction elicited by acetylcholine. Results Rapacuronium displayed a 50-fold higher affinity for antagonism of the M2 versus M3 muscarinic receptor. Moreover, its affinity for the M2 but not the M3 receptor was within concentrations achieved clinically. In addition, rapacuronium caused an increase in baseline tone of airway smooth muscle that was antagonized by atropine but not by previous depletion of nonadrenergic noncholinergic neurotransmitters or by inhibitors of histamine receptors, tachykinin receptors, leukotriene receptors, or calcium channels. Conclusion These findings are consistent with the hypothesis that rapacuronium may precipitate bronchoconstriction by selective antagonism of the M2 muscarinic receptor on parasympathetic nerves, enhancing acetylcholine release to act upon unopposed M3 muscarinic receptors on airway muscle. An additional mechanism of rapacuronium-induced bronchoconstriction is suggested by increases in baseline muscle tension.

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