[Influence of nifedipine on the neuromuscular block produced by atracurium and cistracurium: study in rat phrenic-diaphragmatic nerve preparation.].
OBJECTIVE
Calcium channel blockers may interact with neuromuscular blockers, increasing its effects. Research studies about this interaction display controversial results. In some studies these drugs produced neuromuscular blockage, or contracture, or no effect at all was proved over skeletal neuromuscular response. This study assessed the nifedipine effects over muscular responses and its possible interaction with neuromuscular blockers in rat diaphragm.


METHODS
A number of 25 rats were used, weighing between 250 and 300 g and sacrificed under anesthesia with intraperitoneal pentobarbital (40 mg.kg-1). Preparation was mounted according to the technique described by Bulbring. Diaphragm was kept under tension, connected to an isometric transducer and subjected to an indirect stimulation of 0.1 Hz frequency. Diaphragm contractions were registered on a physiograph. In order to evaluate the effect of these drugs on neuromuscular transmission, they were added separately or associated to the preparation, on the following concentrations: nifedipine (4 microg.mL-1); atracurium (20 microg.mL-1); cistracurium (3 microg.mL-1). On phrenic-nerve preparation, the assessed items were: 1) the extent of diaphragm muscle response to indirect stimulation, before and 45 minutes after adding nifedipine and neuromuscular blockers separately and after the association of both drugs; 2) nifedipine effects on membrane potentials (MP) and miniature end-plate potentials (MEPP).


RESULTS
Employed separately, nifedipine did not alter the extent of muscular responses, but it did significantly increase the neuromuscular blocking activity of atracurium and cistracurium. Nifedipine did not alter the membrane potential and caused an initial increase on MEPP frequencies, followed by a blockage.


CONCLUSIONS
Nifedipine, on the employed concentration, increased the neuromuscular blockage produced by atracurium and cistracurium. Electrophysiological studies demonstrate the existence of presynaptic action and absence of depolarizing action over the muscle fiber.
Sousa
Silmara Rodrigues de
SR
Departamento de Farmacologia, FCM, UNICAMP.
Braga
Angélica de Fátima de Assunção
Ade F
Potério
Glória Maria Braga
GM
Braga
Franklin Sarmento da Silva
FS
Loyola
Yolanda Christina S
YC
Fernandes
Samanta Cristina Antoniassi
SC