This research project is an attempt to clarify the involvement of airway smooth muscle in the experimental model of airway hyperreactivity. This research effort will address this issue in three different directions. First, we will establish experimental models of airway reactivity and we will establish the degree of airway reactivity using an inhalation challenge of histamine and methacholine. Second, this project will identify and define functional alterations of airway smooth muscle from animals with different types of airway hyperreactivity. This will be done by studying contractile characteristics which include both isometric and isotonic contraction of isolated tracheal and bronchial segments. A detailed evaluation of the length-tension and force-velocity relationships will also be done. The electrophysiological properties of airway smooth muscle will be studied as well. These studies will include the measurement of cable properties of normal and altered airway smooth muscle. Third, we will attempt to analyze the possible mechanism(s) of tissue alteration as found after acute sensitization and observed after repeated exposure of sensitizied animals to the inhalation challenge. We will examine the role of the Na+ electrogenic pump and relative ion permeabilities in this change of resting membrane potential. Response to different pharmacological agents which are established in these stimulatory and inhibitory actions as measured by both contractile and electrophysiological changes will be assessed. The issue of airway hyperreactivity is an important clinical issue frequently seen in several airway diseases. The understanding of its mechanism may lead to better and less empirical forms of therapy.
| De, S; Zelazny, E T; Souhrada, J F et al. (1996) Role of phospholipase C and tyrosine kinase systems in growth response of human airway smooth muscle cells. Am J Physiol 270:L795-802 |
| De, S; Zelazny, E T; Souhrada, J F et al. (1995) IL-1 beta and IL-6 induce hyperplasia and hypertrophy of cultured guinea pig airway smooth muscle cells. J Appl Physiol 78:1555-63 |
| De, S; Zelazny, E T; Souhrada, J F et al. (1993) Interleukin-1 beta stimulates the proliferation of cultured airway smooth muscle cells via platelet-derived growth factor. Am J Respir Cell Mol Biol 9:645-51 |
| Souhrada, M; Souhrada, J F (1993) Inhibitory effect of staurosporine on protein kinase C stimulation of airway smooth muscle cells. Am Rev Respir Dis 148:425-30 |
| Souhrada, M; Souhrada, J F (1993) Effect of IgG1 and its fragments on resting membrane potential of isolated tracheal myocytes. J Appl Physiol 74:1948-53 |
