The effects and interactions of pipecuronium and atracurium with diltiazem and verapalmil on the electrically-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat phrenic-hemidiaphragm preparation. Pipecuronium (3X10(-7) -4X10(-6)) and atracurium (10(-6) -3X10(-5) M) decreased the electrically-evoked twitch response, train-of-four and tetanus ratio in a dose-related fashion and the pipecuronium was more potent than atracurium. The inhibitory effects of pipecuronium and atracurium were potentiated by pretreatment of 5 uM diltiazem and verapamil, Ca++-channel blokers, in which the concentration of diltiazem or verapamil has no obvious effect on the twitch response itself. Futhermore, it is noteworthy that the inhibitory effects of pipecuronium and atraeurium were markedly potentiated by 150 uM hemicholinium pretreatment. On the basis of these findings, the results of present study suggests that the muscle relaxation by pipecuronium and atracurium is mediated by pre- and post-junctional receptor blockade, and that diltiazem or verapamil intensifies neuromuscular blockade produced by these musele relaxants. The potentiating effect of diltiazem or verapamil may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.
Acetylcholine ; Animals ; Atracurium ; Calcium ; Diltiazem* ; Hemicholinium 3 ; Muscle Relaxation ; Neuromuscular Blockade* ; Pipecuronium ; Rats ; Tetanus ; Verapamil*

The effects and interactions of pancuronium and vecuronium with diltiazem on the electri- cally-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat hemi-diaphragm preparation. Pancuronium(3 X 10(-7) -10(-5) M) and vecuronium(3 X 10(-6)-15 X 10(-6) M) decreased the electrically evoked(nerve stimulation, 0.1Hz, 0.5ms, 10V) twitch response, train-of-four and tetanus ratio in a dose-related fashion and pancuronium was more potent than vecuronium. The inhibitory effects of pancuronium and vecuronium were potentiated by pretreatment with 5 & 10 uM diltiazem, a Ca++-channel blocker, in which the concentration of diltiazem has no obvious effects on the twitch response itself. Furthermore, it is noteworth that the inhibitory effects of pancuronium and vecuronium were markedly potentiated by 150 uM hemicholinium pretreatment. In cases of the direct(muscle, 0.1 Hz, 5 ms, 10 V) stimulation, pancuronium and vecuronium decreased the electrically evoked twitch response dose dependently, but the amplitudes of inhibition were less than those in indirect(nerve) stimulation. The inhibitory effects were not affected by diltiazem pretreatment except low doses of vecuronium. On the basis of these findings, the result of the present study suggests that the muscle relaxation by pancuronium and vecuronium is mediated by pre- and post-junctional receptor blockade, and that diltiazem intensifies neuromuscular blockade produced by muscle relaxants. The potentiating effect of diltiazem may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.
Acetylcholine ; Animals ; Calcium ; Diltiazem* ; Hemicholinium 3 ; Muscle Relaxation ; Neuromuscular Blockade* ; Pancuronium* ; Rats ; Tetanus ; Vecuronium Bromide*

The effects and interactions of pancuronium and vecuronium with diltiazem on the electri- cally-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat hemi-diaphragm preparation. Pancuronium(3 X 10(-7) -10(-5) M) and vecuronium(3 X 10(-6)-15 X 10(-6) M) decreased the electrically evoked(nerve stimulation, 0.1Hz, 0.5ms, 10V) twitch response, train-of-four and tetanus ratio in a dose-related fashion and pancuronium was more potent than vecuronium. The inhibitory effects of pancuronium and vecuronium were potentiated by pretreatment with 5 & 10 uM diltiazem, a Ca++-channel blocker, in which the concentration of diltiazem has no obvious effects on the twitch response itself. Furthermore, it is noteworth that the inhibitory effects of pancuronium and vecuronium were markedly potentiated by 150 uM hemicholinium pretreatment. In cases of the direct(muscle, 0.1 Hz, 5 ms, 10 V) stimulation, pancuronium and vecuronium decreased the electrically evoked twitch response dose dependently, but the amplitudes of inhibition were less than those in indirect(nerve) stimulation. The inhibitory effects were not affected by diltiazem pretreatment except low doses of vecuronium. On the basis of these findings, the result of the present study suggests that the muscle relaxation by pancuronium and vecuronium is mediated by pre- and post-junctional receptor blockade, and that diltiazem intensifies neuromuscular blockade produced by muscle relaxants. The potentiating effect of diltiazem may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.
Acetylcholine ; Animals ; Calcium ; Diltiazem* ; Hemicholinium 3 ; Muscle Relaxation ; Neuromuscular Blockade* ; Pancuronium* ; Rats ; Tetanus ; Vecuronium Bromide*

This study was aimed at investigation of the stimulatory innervations on the rat urinary bladder. Detrusor muscle strips of 15 mm long were suspended in isolated muscle chambers containing 1 ml of PSS maintained at 37℃ and aerated with 95% O²/5% Co². Isometric myography was performed, and the results were as followings: Muscle strips showed “on-contraction” by electric field stimulation (EFS) frequency-dependently. The EFS-induced contraction was not affected by hexamethonium, a ganglion blocker, but abolished by tetrodotoxin, a nerve conduction blocker. Physostigmine, a cholinesterase inhibitor enhanced the EFS-induced contraction which was inhibited by hemicholinium, an inhibitor of choline uptake at the cholinergic nerve ending. Such an EFS-induced contraction was antagonized by atropine only partially, and the atropine-resistant portion was completely abolished by the desensitization of purinergic receptors by prolonged incubating of the strips in the presence of high concentration of ATP. Bethanechol, a cholinergic agonist, elicited concentration-dependent contraction. Adenosine triphosphate (ATP), a purinergic agonist, induced a weak but concentration-dependent contraction of short duration. Bethanechol-induced contraction was not affected by ATP-desensitization, and ATP-induced contraction was not affected by tetrodotoxin. These results suggest that there are at least two main stimulatory components of innervations in the detrusor muscle, cholinergic muscarinic and purinergic; and those receptors are independent each other.
Adenosine Triphosphate ; Animals ; Atropine ; Bethanechol ; Choline ; Cholinergic Agonists ; Cholinesterases ; Ganglion Cysts ; Hemicholinium 3 ; Hexamethonium ; Myography ; Nerve Endings ; Neural Conduction ; Physostigmine ; Rats* ; Receptors, Purinergic ; Tetrodotoxin ; Urinary Bladder*