Korean J Anesthesiol.  2000 Sep;39(3):381-391. 10.4097/kjae.2000.39.3.381.

The Inhibitory Effects of Midazolam and Diazepam on Smooth Muscle Tension in Rat Trachea

• Kim TK
• Kim HJ
• Shin YS
• Yoon SH
• Park JW

• KMID: 2237605
• DOI: http://doi.org/10.4097/kjae.2000.39.3.381

Abstract

BACKGROUND: It has been demonstrated that a group of minor tranquilizers, benzodiazepines, are able to relax airway smooth muscle, but the mechanism by which these agents produce muscle relaxation are not fully understood. This study was undertaken to determine the effects and mechanism of diazepam and midazolam on Ca2+ and K+ channel in isolated rat trachea muscles by measuring isometric tension.
METHODS
Our experiment was performed to evaluate the effects of midazolam and diazepam by cumulative administration from 10(-6)M to 3 x 10(-5)M to tracheal smooth muscle contraction which was induced by contractile agonists such as ACh 10(-5)M, carbachol 3 x 10(-7)M, and KCl 40 mM. The effects of midazolam and diazepam were evaluated on Ca2+ and K+ channels by inhibition of contraction using a nonspecfic K+ channel blocker such as tetraethyl ammonium (TEA) elicited by a 2 mM Ca2+ space addition to Ca2+ free on high K+ depolarizing rat tracheal muscle. Also, to elucidate any mechanism involved, the effects of flumazenil (a specific central antagonist of benzodiazepines), propranolol (a beta adrenergic antagonist), and atropine (a muscarinic antagonist) and tracheal epithelium removal were examined.
RESULTS
In a concentration-dependent way, both midazolam and diazepam relaxed airway smooth muscle directly and had inhibitory effects on voltage-dependent Ca2+ (VDCC) and K+ channels.
CONCLUSIONS
These results suggest that benzodiazepines relax airway smooth muscle, not via a neural pathway or benzodiazepine receptor but through a direct action on Ca2+ and K+channels. Benzodiazepine enhanced K+ conductance, leading to a decrease in VDCC opening, thus reducing Ca2+ through the voltage-dependent Ca2+ channel, in addition to inhibiting of intracellular Ca2+ release.

Keyword

Anesthetics, intravenous: diazepam; midazolam; Airway: trachea; smooth muscle; Ions: Ca2+ channel; K+ channel; Pharmacology: tetraethyl ammonium

MeSH Terms

Ammonium Compounds
Animals
Atropine
Benzodiazepines
Calcium Channels
Carbachol
Diazepam*
Epithelium
Flumazenil
Midazolam*
Muscle Relaxation
Muscle, Smooth*
Muscles
Neural Pathways
Propranolol
Rats*
Receptors, GABA-A
Trachea*
Atropine
Benzodiazepines
Calcium Channels
Carbachol
Diazepam
Flumazenil
Midazolam
Propranolol
Receptors, GABA-A