Earlier work by the principal investigator and his associates has demonstrated that the removal of the bronchial epithelium causes hyperresponsiveness of canine airway smooth muscle. The principal goals of the proposed research are: (a) to continue to define the extent of the modulation by the epithelium of the responsiveness of airway smooth muscle in health and disease (asthma); (b) to determine the identity of the bronchoactive factors secreted by the epithelial cells; and (c) to start to explore interactions between epithelium and pulmonary blood vessels. Tissues of the dog and the guinea-pig will be studied throughout the projected five year period; certain experiments will be performed on material from sheep and humans (as available). The proposed approach involves mainly physiological (measurement of contractile responses, bioassay studies, electrophysiological studies) and pharmacological studies, although in certain series biochemical (measurement of metabolites of arachidonic acid, levels of cyclic nucleotides) and histological determinations will be prfomred. It is expected that the proposed research will increase our understanding of the factors which affect bronchial tone, and in particular improve our knowledge of the interactions between the different cells in the bronchial wall which can play a role in the increased reactivity of the airways observed in obstructive lung disease and bronchial asthma. The studies on pulmonary blood vessels should help to explain how changes in pulmonary vascular responsiveness may lead to alterations in the ventilation-perfusion ratio, and possibly provide an explanation for hypoxic pulmonary vasoconstriction.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory and Applied Physiology Study Section (RAP)
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Mayo Clinic, Rochester
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Gao, Y; Vanhoutte, P M (1994) Epithelium acts as a modulator and a diffusion barrier in the responses of canine airway smooth muscle. J Appl Physiol 76:1843-7
Gao, Y; Vanhoutte, P M (1993) Products of cyclooxygenase mediate the responses of the guinea pig trachea to hydrogen peroxide. J Appl Physiol 74:2105-11
Gao, Y; Vanhoutte, P M (1993) Respiratory epithelium modulates the responses of canine bronchi to cooling. J Appl Physiol 74:2421-5
Gao, Y; Vanhoutte, P M (1993) Responsiveness of the guinea pig trachea to stretch: role of the epithelium and cyclooxygenase products. J Appl Physiol 75:2112-6
Gao, Y; Vanhoutte, P M (1993) Attenuation of contractions to acetylcholine in canine bronchi by an endogenous nitric oxide-like substance. Br J Pharmacol 109:887-91
Morrison, K J; Vanhoutte, P M (1992) Characterization of muscarinic receptors that mediate contraction of guinea-pig isolated trachea to choline esters: effect of removing epithelium. Br J Pharmacol 106:672-6
Gao, Y; Vanhoutte, P M (1992) Hypotonic solutions induce epithelium-dependent relaxation of isolated canine bronchi. Lung 170:339-47
Gao, Y; Vanhoutte, P M (1992) Effects of hydrogen peroxide on the responsiveness of isolated canine bronchi: role of prostaglandin E2 and I2. Am J Physiol 263:L402-8
Morrison, K J; Vanhoutte, P M (1991) Inhibition of airway smooth muscle tone by a phorbol ester in the guinea pig trachea: role of epithelium and receptor reserve of the contractile agent. J Pharmacol Exp Ther 259:198-204
Gao, Y S; Vanhoutte, P M (1989) Lowering Po2 induces epithelium-dependent relaxation in isolated canine bronchi. Am J Physiol 257:C1034-7