Effects of Nerve Stimulation in Mouse Lungs

Abstract

Mouse pulmonary airways and blood vessels are innervated by autonomic and sensory nerves. Stimulation of mouse pulmonary nerves can activate a variety of neurotransmitter systems to control airway and blood vessel diameter. The objective of this study was to identify the neurotransmitter systems causing constriction and/or dilatation of mouse airways and pulmonary arteries. Precision cut lung slices from CF‐1 mice were exposed to electric field stimulation (EFS) using parameters known to activate neurotransmitter release (1.0 ms, 50 V, 1–30 Hz). Changes in airway or pulmonary artery luminal area were captured as video images and quantified using ImageJ. EFS caused constriction in both airways and pulmonary arteries in a frequency‐dependent manner. Maximum constriction to 30 Hz EFS was 52.8 ± 3.5% in airways and 42.4 ± 3.7% in pulmonary arteries. Interestingly, the ability of the muscarinic receptor antagonist atropine to block EFS induced constriction in airways was frequency dependent. In airways, 1 μM atropine blocked 70.6 ± 19.2% of EFS induced constriction at 3 Hz, but only blocked 22.1 ± 12.6% of EFS induced constriction at 30 Hz. Treatment of pulmonary arteries with 1 μM prazosin, an α1‐adrenoceptor antagonist, reduced constriction by 62.6 ± 12.3% at 30 Hz EFS. These data are consistent with parasympathetic constriction of airways by acetylcholine and sympathetic constriction of pulmonary arteries by norepinephrine. In addition, an atropine‐resistant EFS constriction in airways and a prazosin‐resistant EFS constriction in pulmonary arteries were identified. Understanding the neurotransmitter systems causing nerve mediated constriction and/or dilatation of airways and pulmonary arteries may identify novel therapeutic targets for treatment of asthma, pulmonary hypertension, and other lung diseases.Support or Funding InformationSupported by NIH R01HL116849 and Nebraska State LB595 to Y. Tu and P.W. Abel