Regulation of spontaneous tone in guinea pig trachea

Asthma is a common disease, characterized by periods of bronchoconstriction of unclear origin. This thesis examines a specific behavior of airway smooth muscle, the so-called spontaneous airway tone. It was suspected that a defect regulation of this tone may be a cause of asthmatic bronchoconstriction. The experiments shows that tracheal preparations can display two types of spontaneous tone. In traditionally high (94 %) oxygen, preparations display a strong, smooth, irregular type of tone, while in 12 %, they display a weaker, regularly oscillating spontaneous tone. The different behavior was found to be caused by the neuroepithelial endocrine (NEE) cells releasing powerful relaxing and contracting factors only in low oxygen environments. Capsaicin, the pungent principal of red peppers, was found to be able to strongly suppress both types of tone. This effect is proposed to be caused by a reduction of the release of substance P from the sensory C-fibers. Substance P is believed to be the "motor" of the spontaneous tone, and it appears to act through a new receptor, that is resistant to the blocking effect by presently available tachykinin antagonists. Interestingly, it proves that some inhibitory nerves, that are important for the development of the spontaneous airway tone, are resistant to the blocking action of tetrodotoxin. It is argued that the oscillating spontaneous tone in 12 % oxygen is physiologically normal. Furthermore, the findings that the NEE cells release powerful relaxing and contracting factors, and the suggestion that substance P stimulates the tone through a new substance P receptor, may result in new therapies for asthma.