OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways.METHODS Murine precision cut lung slices(PCLS)and trachea were prepared,placed into perf...OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways.METHODS Murine precision cut lung slices(PCLS)and trachea were prepared,placed into perfusion chambers equipped with platinum electrodes and stimulated transmurally(1.0 ms,50 V,0.1-30 Hz).To measure PCLS constriction,changes in airway luminal area in response to electric field stimulation(EFS)were captured as video images quantified using Image J software.For trachea,changes in isometric tension were recorded using Grass force transducers.Frequency response curves were generated in the absence and the presence of the inhibitors magnesium,atropine and capsaicin and responses analyzed and compared using a student's t-test(P<0.05).RESULTS EFS caused airway constriction in a frequency-dependent manner that was best fit by a biphasic curve.Neuron-specific stimulation was verified by Mg^(2+) blockade.Maximum airway constriction to 30 Hz EFS in PCLS was(51.8±3.0)%while tracheal constriction averaged(551±80)mg.Interestingly,in PCLS the muscarinic receptor antagonist atropine(10μmol·L^(-1))blocked(99.5±7.2)%of EFS induced constriction at 1 Hz,but only blocked(23.3±3.8)%of EFS induced constriction at 30 Hz and eliminated the first phase but not the second phase of the biphasic EFS response.Treatment with capsaicin to deplete sensory neurotransmitters significantly increased EFS constriction supporting the presence of sensory neurotransmitter systems in airways.CONCLUSION These data are consistent with parasympathetic constriction of airways by acetylcholine at lower EFS frequencies while higher frequencies release sensory dilator neurotransmitters.These data provide evidence for multiple nerve types innervating airways which may provide novel targets for treatment of lung disease.展开更多
INTRODUCTION Congenital vascular rings （VRs） are a group of rare cardiovascular anomalies that result from abnormal embryonic development of the paired aortic arches or branching pulmonary arteries. Clinical present...INTRODUCTION Congenital vascular rings （VRs） are a group of rare cardiovascular anomalies that result from abnormal embryonic development of the paired aortic arches or branching pulmonary arteries. Clinical presentation of VR depends on its anatomy, degree, and site of compression.展开更多
文摘OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways.METHODS Murine precision cut lung slices(PCLS)and trachea were prepared,placed into perfusion chambers equipped with platinum electrodes and stimulated transmurally(1.0 ms,50 V,0.1-30 Hz).To measure PCLS constriction,changes in airway luminal area in response to electric field stimulation(EFS)were captured as video images quantified using Image J software.For trachea,changes in isometric tension were recorded using Grass force transducers.Frequency response curves were generated in the absence and the presence of the inhibitors magnesium,atropine and capsaicin and responses analyzed and compared using a student's t-test(P<0.05).RESULTS EFS caused airway constriction in a frequency-dependent manner that was best fit by a biphasic curve.Neuron-specific stimulation was verified by Mg^(2+) blockade.Maximum airway constriction to 30 Hz EFS in PCLS was(51.8±3.0)%while tracheal constriction averaged(551±80)mg.Interestingly,in PCLS the muscarinic receptor antagonist atropine(10μmol·L^(-1))blocked(99.5±7.2)%of EFS induced constriction at 1 Hz,but only blocked(23.3±3.8)%of EFS induced constriction at 30 Hz and eliminated the first phase but not the second phase of the biphasic EFS response.Treatment with capsaicin to deplete sensory neurotransmitters significantly increased EFS constriction supporting the presence of sensory neurotransmitter systems in airways.CONCLUSION These data are consistent with parasympathetic constriction of airways by acetylcholine at lower EFS frequencies while higher frequencies release sensory dilator neurotransmitters.These data provide evidence for multiple nerve types innervating airways which may provide novel targets for treatment of lung disease.
文摘INTRODUCTION Congenital vascular rings （VRs） are a group of rare cardiovascular anomalies that result from abnormal embryonic development of the paired aortic arches or branching pulmonary arteries. Clinical presentation of VR depends on its anatomy, degree, and site of compression.
