The overall goal of this project will continue to be the investigation of physiological mechanisms regulating airway reactivity under two conditions: (1) in vivo antigen-induced hypersensitivity, and (2) after exsanguination. Based on our previously reported observations and additional preliminary data, six hypotheses may be postulated;
the aims are to test these hypotheses. This proposal is designed to carry out the aims as follows. (1) The relationship between the nonadrenergic noncholinergic (NANC) inhibitory system and antigen-induced bronchoconstriction will be examined. In pilot studies, oxyhemoglobin has been found to suppress the NANC relaxation in the guinea pig trachea in vitro, and to enhance airway spasm during antigen challenge in vivo. More studies will be performed to establish and quantitate this relationship. (2) Substance P depletion has been shown by others to desensitize airways. We will explore whether depletion of substance P can also reduce bronchial hyperreactivity following antigen challenge. (3) The importance of leukotrienes (LT, SRS-A) which are postulated mediators of antigen-induced airway constriction, will be studied by enhancement or inhibition of LT function during antigen-induced hypersensitivity. (4) Characteristics of the postmortem bronchoconstriction (a type of non-immunologically induced bronchial hyperreactivity) that we have been studying in the guinea pig lung will be further defined in terms of similarity to antigen-induced airway constriction, relationship to substance P, and sites of airway spasm.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034269-03
Application #
3346991
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1984-09-01
Project End
1987-12-31
Budget Start
1986-07-01
Budget End
1987-12-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Schools of Pharmacy
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Lai, Y L (1990) Oxygen radicals in capsaicin-induced bronchoconstriction. J Appl Physiol 68:568-73
Lai, Y L (1988) Maximal expiratory flow in the guinea pig. Lung 166:303-13
Ko, W C; Lai, Y L (1988) The tracheal nonadrenergic noncholinergic inhibitory system during antigen challenge. Respir Physiol 74:129-38
Ko, W C; Lai, Y L (1988) Cyclic GMP affecting the tracheal nonadrenergic noncholinergic inhibitory system. Respir Physiol 73:351-62
Lai, Y L; Ganesan, S; Lai-Fook, S J (1988) Airway resistance measured in liquid-trapped guinea pig lungs by micropuncture. J Appl Physiol 65:2446-52
Lai, Y L (1987) Fluid trapping in postmortem guinea pig lungs. Lung 165:213-23
Lai, Y L (1987) Calcium dependency of massive postmortem bronchoconstriction in guinea pig lungs. Respir Physiol 68:41-51
Lai, Y L; Cornett, A F (1987) Substance P-inducing massive postmortem bronchoconstriction in guinea pig lungs. J Appl Physiol 62:746-51