Airway smooth muscle orientation in intraparenchymal airways

Abstract

Airway smooth muscle (ASM) shortening is the central event leading to bronchoconstriction. The degree to which airway narrowing occurs as a consequence of shortening is a function of both the mechanical properties of the airway wall as well as the orientation of the muscle fibers. Although the latter is theoretically important, it has not been systematically measured to date. The purpose of this study was to determine the angle of orientation of ASM (theta) in normal lungs by using a morphometric approach. We analyzed the airway tree of the left lower lobes of four cats and one human. All material was fixed with 10% buffered Formalin at a pressure of 25 cmH2O for 48 h. The fixed material was dissected along the airway tree to permit isolation of generations 4-18 in the cats and generations 5-22 in the human specimen. Each airway generation was individually embedded in paraffin. Five-micrometer-thick serial sections were cut parallel to the airway long axis and stained with hematoxylin-phloxine-saffron. Each block yielded three to five sections containing ASM. To determine theta, we measured the orientation of ASM nuclei relative to the transverse axis of the airway by using a digitizing tablet and a light microscope (x250) equipped with a drawing tube attachment. Inspection of the sections revealed extensive ASM crisscrossing without a homogeneous orientation. The theta was clustered between -20 degrees and 20 degrees in all airway generations and did not vary much between generations in any of the cats or in the human specimen. When theta was expressed without regard to sign, the mean values were 13.2 degrees in the cats and 13.1 degrees in the human. This magnitude of obliquity is not likely to result in physiologically important changes in airway length during bronchoconstriction.

Contractility and Ca2+ Signaling of Smooth Muscle Cells in Different Generations of Mouse Airways

“…These include differences in the cellular characteristics of individual SMC, the mass of SMCs, or the elastic resistance of the airway wall that opposes contraction. For example, several studies have demonstrated differences in the receptor density or receptor types on the surface of SMCs (24)(25)(26)(27), the ratio of SMCs to the airway area (28)(29)(30), the stiffness of airway wall (31,32), and orientation of the SMCs (29,30,33,34). In addition, the airways may also be influenced differentially by the epithelia-derived relaxing factors (35,36).…”

Physiological Mechanisms of Airway Hyperresponsiveness in Obese Asthma

“…For example, ASM cells are typically not aligned perfectly circumferentially around the airway but instead assume a variety of angles relative to the circumference (31). How shortening of these cells translates into airway narrowing depends on the relative stiffnesses of the airway wall in the radial and axial directions (32), both of which might conceivably be altered by airway remodeling.…”

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…However, the strain profile must be altered in the presence of elevated ASM tone and with airway narrowing, such as that occurs in asthma. As ASM is predominantly oriented circumferentially about the airways with an average pitch close to 13u [252], increased tone would increase circumferential stiffness relative to the stiffness along the length of the airway. Thus, the stretch proffered by breathing would tend to be more axial than circumferential, leading to development of strain anisotropy in vivo.…”