The prevalence and expression of asthma is greater during childhood than in adult life. Studies indicate that airway reactivity in several species increases from minimal levels during fetal life and birth to a substantial level in a few days to weeks. While reasons for this difference are unclear, prior investigations have focused on the mechanical instability of juvenile airways and the greater frequency and impact of inflammatory stimuli such as viral pathogens and allergic sensitization. More recent studies emphasized the role of airway smooth muscle (ASM). Allergic sensitization has been shown greatly to increase shortening velocity (VS) and maximal shortening in ASM. Early allergic sensitization may contribute to the increased reactivity in immature airways and confer permanent hyperresponsiveness by altering normal maturational changes in the contractile phenotype of ASM. The application proposes to investigate the mechanism of maturational changes in ASM contractility at baseline and after allergic sensitization. The hypotheses are: 1) Juvenile ASM has increased VS compared to infant or adult ASM due to differences in opposing contractile properties: increases in myosin light chain kinase (MLCK) concentration in juveniles without a synchronous increase in internal resistance of shortening (IRS) until adult life. 2) Allergic sensitization with ovalbumin (OA) in juveniles further increases contractility by increasing levels of MLCK and preventing the normal increase in IRS. 3) The consequence of early sensitization is a further increase in VS that persists into adult life.
The specific aims are: 1) Determine the effect of ontogeny on airway smooth muscle shortening; and 2) Determine the effect of allergic sensitization on the ontogeny of shortening.
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| Chitano, Pasquale; Wang, Lu; Murphy, Thomas M (2005) Mechanisms of airway smooth muscle relaxation during maturation. Can J Physiol Pharmacol 83:833-40 |
| Wang, Lu; Chitano, Pasquale; Murphy, Thomas M (2005) Maturation of guinea pig tracheal strip stiffness. Am J Physiol Lung Cell Mol Physiol 289:L902-8 |
| Wang, Lu; Chitano, Pasquale; Murphy, Thomas M (2005) Length oscillation induces force potentiation in infant guinea pig airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 289:L909-15 |
| Wang, Lu; Chitano, Pasquale; Murphy, Thomas M (2005) A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation. Can J Physiol Pharmacol 83:817-24 |
| Chitano, Pasquale; Worthington, Charles L; Jenkin, Janet A et al. (2005) Ontogenesis of myosin light chain phosphorylation in guinea pig tracheal smooth muscle. Pediatr Pulmonol 39:108-16 |
| Bai, Tony R; Bates, Jason H T; Brusasco, Vito et al. (2004) On the terminology for describing the length-force relationship and its changes in airway smooth muscle. J Appl Physiol 97:2029-34 |
| Chitano, Pasquale; Voynow, Judith A; Pozzato, Valeria et al. (2004) Ontogenesis of myosin light chain kinase mRNA and protein content in guinea pig tracheal smooth muscle. Pediatr Pulmonol 38:456-64 |
| Chitano, P; Murphy, T M (2003) Maturational changes in airway smooth muscle shortening and relaxation. Implications for asthma. Respir Physiol Neurobiol 137:347-59 |
| Chitano, Pasquale; Cox, Carrie M; Murphy, Thomas M (2002) Relaxation of guinea pig trachealis during electrical field stimulation increases with age. J Appl Physiol 92:1835-42 |
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