Pharmacologic modulation of antigen-induced pulmonary responses in the perfused guinea pig lung.
The effect of various enzyme inhibitors and receptor antagonists on antigen (ovalbumin)-induced changes in pulmonary hemodynamics (arterial pressure, capillary pressure, and arterial and venous resistance), fluid filtration, and airway reactivity were monitored for 60 min in recirculating Ringer's-perfused, actively sensitized lungs. Bolus ovalbumin (30 micrograms) injection into the pulmonary artery produced initial (3 min postovalbumin) increases in pulmonary arterial pressure of 68 +/- 9% above baseline, which were followed by secondary increases (143 +/- 45% above baseline) at 30 min postovalbumin. Ovalbumin challenge also caused initial increases in pulmonary capillary pressure, arterial resistance, and venous resistance within 3 min after administration (100 +/- 34%, 51 +/- 10%, and 221 +/- 77% above baseline, respectively), which were further elevated at the end of the 60-min experimental period (292 +/- 74%, 66 +/- 29%, and 559 +/- 61% above baseline, respectively). Ovalbumin-induced increases in intratracheal pressure (771 +/- 142% above baseline) peaked at 3 min postchallenge and gradually returned towards baseline. Ovalbumin-induced changes in lung weight increased gradually over the perfusion period (3.5 +/- 1.0 g above baseline at 60 min postovalbumin). Antigen-induced changes in pulmonary arterial pressure, intratracheal pressure, and lung weight were abolished by pretreatment with the histamine1-receptor antagonist, pyrilamine (1 microM). The cyclooxygenase inhibitor, indomethacin (1 microM), potentiated antigen-induced secondary increases in pulmonary arterial pressure, intratracheal pressure, and lung weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Selig
W M
WM
Hoffmann-La Roche, Bronchopulmonary Research, Nutley, NJ 07110.
Tocker
J E
JE
Tannu
S A
SA
Cerasoli
F
F
Durham
S K
SK
D000818:Animals; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007114:Immunization / Q000379:methods; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010477:Perfusion / Q000379:methods; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011654:Pulmonary Edema / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D015777:Eicosanoids; D010047:Ovalbumin