Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent [chapter]

Ynuk Boss, Peter D., Yohan Boss
2012 Lung Diseases - Selected State of the Art Reviews  
It is worth-mentionning that the ASM has also been shown to proliferate, to migrate, to express adhesion molecules and receptors interacting with immune cells, as well as to synthesize extracellular matrix components, cytokines and chemokines. Most of these ASM functions were studied in monolayers of ASM cells in culture. More evidences are eagerly needed to confirm the existence of these ASM functions in vivo. However, if they happen in vivo, their relevance to asthma pathogenesis is
more » ... enesis is unquestionable. These subjects have been reviewed lately and will not be addressed in the present chapter (18, 50, 72). Force The load impeding ASM shortening is auxotonic; i.e., it increases progressively as the muscle shortens. It is thus logical that greater force would lead to more shortening and concomitantly more airway narrowing. That is the reason why the force-generating capacity of ASM is such an important determinant of airway responsiveness. The force-generating capacity also matters because it influences other ASM contractile properties. The relationship between the load and the velocity can be fitted with an exponential decay equation; so that increasing the load decreases the shortening velocity exponentially. This implies that a stronger muscle would counteract a given load faster and would thus shorten faster. In a context where the muscle is subjected to contract under a progressively increasing load, as it occurs in vivo, a stronger muscle would also shorten further. This is because a muscle able to produce more force at any given length would allow the shortening to progress further before reaching a load equal to its force. A stronger muscle would also increase ASM stiffness, which, as discussed below (subsection 2.2), can have an important impact on in vivo airway responsiveness. The force or stress, which is the force per cross-sectional area, produced by the ASM depends on the potency and the concentration of the contractile stimulus involved. The relationship between spasmogen concentration and ASM-force can be described by a sigmoidal equation. So, in vivo, the amount of spasmogen reaching the ASM is one of the main determinants of the force produced by the muscle. The force produced by the ASM is also dictated by its length. Longer muscle generally generates more force in response to a given contractile stimulus (86, 154, 259, 261) . In fact, the decrease in ASM-force caused by length reduction is proportional to he magnitude of the length change (103). Hence, in situ factors affecting the operating length of the ASM can be of considerable importance in the understanding of AHR, but that will be discussed later in this chapter (subsection 4.1.5). Regardless of the aforementioned factors, the force can also be determined by the muscle's intrinsic capacity to generate force. So for a given concentration of a chosen spasmogen and a given length, the stress produced by the muscle can be different. This has led some to suggest that ASM derived from asthmatics may produce more stress than ASM derived from non-asthmatics, and that might be the cause of AHR. This hypothesis has been tested by several groups now and, although still debatable, the bulk of evidence suggests that the stress-generating capacity of asthmatic and non-asthmatic ASM is the same (reviewed in (153)). Taken together, the force-generating capacity of the ASM is certainly an important determinant of airway responsiveness, but no data published thus far convincingly demonstrate that this contractile property is altered in asthma. Stiffness In the field of ASM the term 'stiffness' certainly has different connotations. By definition stiffness is the amount of force required to cause a given change in length. The stiffness of Lung Diseases -Selected State of the Art Reviews
doi:10.5772/29724 fatcat:43wj3icyhrhwpkq46jnss4up7q