Effect of dexmedetomidine on spontaneous contraction of colon smooth muscles of rabbits in vitro

Abstract

Objective To investigate the effect of dexmedetomidine on the spontaneous contraction of colon smooth muscles of rabbits. Methods Healthy rabbits of both sexes, aged 2-3 months, weighing 1.8-2.3 kg, were sacrificed to prepare colon smooth muscle specimens which were incubated with the K-H solution.Treatment with drugs was performed after incubation was stable(baseline). ExperimentⅠ Six colon segments were selected, and dexmedetomidine was accumulatively added to the K-H solution with the final concentrations of 1, 10, 20, 40, 60 80 and 100 nmol/L in sequence.Experiment Ⅱ Six colon segments were selected, dexmedetomidine was added to the K-H solution(final concentration 60 nmol/L), and the colon segments were incubated for 3 min followed by washout, NG-nitro-L-arginine methyl ester(final concentration 100 mmol/L)was then added to the K-H solution, the colon segments were then incubated for 10 min, and then dexmedetomidine(final concentration 60 nmol/L)was added again.Experiment Ⅲ Twelve colon segments were randomly divided into 2 groups(n=6 each)using a random number table: CaCl2 group and dexmedetomidine+ CaCl2 group.The culture medium was replaced with calcium-free K-H solution, and 5 min later CaCl2(final concentration 1.8 mol/L)was added in CaCl2 group.The culture medium was replaced with calcium-free K-H solution, the colon segments were incubated for 5 min, dexmedetomidine(final concentration 60 nmol/L)was added, the colon segments were then incubated for 10 min, and then CaCl2(final concentration 1.8 mol/L)was added in dexmedetomidine+ CaCl2 group.Experiment Ⅳ Twelve colon segments were randomly divided into 2 groups(n=6 each)using a random number table: ryanodine group and dexmedetomidine+ ryanodine group.The culture medium was replaced with calcium-free K-H solution, the colon segments were incubated for 5 min, and then ryanodine(final concentration 0.2 mmol/L)was added in ryanodine group.The culture medium was replaced with calcium-free K-H solution, the colon segments were incubated for 5 min, dexmedetomidine(final concentration 60 nmol/L)was added, the colon segments were then incubated for 10 min, and then ryanodine(final concentration 0.2 mmol/L)was added in dexmedetomidine+ ryanodine group.The colon segments were connected to a tension transducer and placed in oxygen-saturated K-H solution, and BL-420F biological signal processing system was used to record the amplitude and frequency of the spontaneous contraction of colon smooth muscles at baseline and during incubation with drugs. Results Dexmedetomidine decreased the amplitude of spontaneous contraction of colon smooth muscles in a dose-dependent manner and produced no effect on the frequency of spontaneous contraction.NG-nitro-L-arginine methyl ester alone produced no effect on the amplitude and frequency of the spontaneous contraction of colon smooth muscles, but weakened the inhibitory effect of dexmedetomidine on the amplitude of spontaneous contraction.The amplitude and frequency of the spontaneous contraction of colon smooth muscles were significantly decreased during incubation with calcium-free K-H solution, and CaCl2 and ryanodine raised the amplitude and frequency of the spontaneous contraction of colon smooth muscles.Dexmedetomidine preadministration significantly inhibited CaCl2- and ryanodine-induced increase in the amplitude or frequency of the spontaneous contraction of colon smooth muscles. Conclusion Dexmedetomidine can inhibit the spontaneous contraction of colon smooth muscles of rabbits in vitro, and the mechanism may be related to activation of nitric oxide and inhibition of extracellular calcium inflow and intracellular calcium release. Key words: Dexmendetomidine; Colon; Smooth muscle; Muscle contraction