Skeletal muscle relaxants inhibit rat tracheal smooth muscle tone in vitro.

Neuromuscular blocking drugs (NMBD) can inhibit not only nicotinic but also muscarinic (M) receptors and thereby affect not only skeletal but also smooth muscle (SM) tone. A selective postjunctional muscarinic inhibition would relax, while prejunctional inhibition of muscarinic M2 receptor might hasten SM contraction thereby increasing the risk of bronchospasm. In rat tracheal rings in vitro we evaluated the effects of cumulative concentrations of some NMBD and M receptor blocking agents for their effects on tracheal smooth muscle (TSM) tone pre-contracted with carbachol (CARB; 5 x 10(-7)M or 10(-6)M), pilocarpine (PILO; 5 x 10(-6)M), or by electrical field stimulation. The NMBDs produced relaxation in the preparations precontracted with CARB or PILO. The order of potency after CARB (10(-6)M) was (EC(50)): 4-DAMP (9.8) >atropine (9.2) >methoctramine (6.4) >pancuronium (6.0) >mivacurium (5.8) >cisatracurium (5.6) >gallamine (5.2) >rocuronium (4.8) >succinylcholine (2.9); NMBDs also partially prevented contraction elicited by the electrical field stimulation. We demonstrated that the clinically used NMBD that were examined produced rat TSM relaxation, probably by predominantly blocking postjunctional muscarinic receptors.

[1]  F. Mack,et al.  Adaptation of myosin heavy chain mRNA expression after implantation of poly(3)hydroxybutyrate scaffolds in rat m. latissimus dorsi. , 2008, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[2]  R. Raikova,et al.  Force generated by fast motor units of the rat medial gastrocnemius muscle during stimulation with pulses at variable intervals. , 2008, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[3]  Y. Atoji,et al.  Nerve plexuses in the trachea and extrapulmonary bronchi of the rat. , 2004, Archives of histology and cytology.

[4]  C. Hirshman,et al.  A Mechanism for Rapacuronium-induced Bronchospasm: M2 Muscarinic Receptor Antagonism , 2003, Anesthesiology.

[5]  M. Schreiner,et al.  Rapacuronium and the Risk of Bronchospasm in Pediatric Patients , 2002, Anesthesia and analgesia.

[6]  J. McArdle,et al.  Advances in Neurobiology of the Neuromuscular Junction: Implications for the Anesthesiologist , 2002, Anesthesiology.

[7]  H. Meurs,et al.  Identification, localization and function of muscarinic receptor subtypes in the airways , 2001 .

[8]  D Curran-Everett,et al.  Multiple comparisons: philosophies and illustrations. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[9]  K. Rehder,et al.  Do pipecuronium and rocuronium affect human bronchial smooth muscle? , 1999, Anesthesiology.

[10]  R. Goldie,et al.  Muscarinic cholinoceptor subtypes mediating tracheal smooth muscle contraction and inositol phosphate generation in guinea pig and rat. , 1999, European journal of pharmacology.

[11]  H. Sakai,et al.  Characterization of muscarinic receptors in rat bronchial smooth muscle in vitro. , 1998, Research communications in molecular pathology and pharmacology.

[12]  K. Sumikawa,et al.  Steroidal muscle relaxants attenuate the contractile and phosphatidylinositol responses of rat trachea. , 1998, Research communications in molecular pathology and pharmacology.

[13]  C. Hirshman,et al.  Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. , 1998, Anesthesiology.

[14]  M. Fournier,et al.  Effects of corticosteroids on epithelial structure and smooth muscle function of rat trachea. , 1998, The European respiratory journal.

[15]  N. Toda,et al.  Comparison of the Effects of Pancuronium and Vecuronium in Canine Coronary and Renal Arteries , 1998, Anesthesiology.

[16]  R. Eglen,et al.  Muscarinic receptor subtypes and smooth muscle function. , 1996, Pharmacological reviews.

[17]  K. Sumikawa,et al.  Anticholinesterase Drugs Stimulate Phosphatidylinositol Response in Rat Tracheal Slices , 1996, Anesthesia and analgesia.

[18]  J. Lammers,et al.  Pancuronium masks the prejunctional muscarinic autoreceptor in guinea pig tracheal smooth muscle. , 1995, Life sciences.

[19]  M. Yacoub,et al.  Evidence for prejunctional muscarinic autoreceptors in human and guinea pig trachea. , 1995, American journal of respiratory and critical care medicine.

[20]  J. Moss.  Muscle relaxants and histamine release , 1995, Acta anaesthesiologica Scandinavica. Supplementum.

[21]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[22]  D. Lambert,et al.  Studies on the interaction of steroidal neuromuscular blocking drugs with cardiac muscarinic receptors. , 1994, British journal of anaesthesia.

[23]  I. Hall,et al.  Expression of muscarinic M2 receptors in cultured human airway smooth muscle cells. , 1993, American journal of respiratory cell and molecular biology.

[24]  C. Hirshman,et al.  M2 muscarinic receptors inhibit isoproterenol-induced relaxation of canine airway smooth muscle. , 1992, The Journal of pharmacology and experimental therapeutics.

[25]  S. Basta.  Clinical pharmacology of mivacurium chloride: a review. , 1992, Journal of clinical anesthesia.

[26]  E. Vizi,et al.  In vitro comparison of the neuromuscular antinicotinic and intestinal antimuscarinic effects of different nondepolarizing muscle relaxants. , 1989, Archives internationales de pharmacodynamie et de therapie.

[27]  R. Townley,et al.  Comparison of muscarinic and beta adrenergic receptors between bovine peripheral lung and tracheal smooth muscles: a striking difference in the receptor concentration. , 1982, Life sciences.