Cyclic nucleotides of lung lavage following acute antigen exposure in chronically exposed sheep

In the sheep model of chronic allergic airway disease, we measured sequentially for 7 h following antigen exposure (Ascaris suum) histamine and the cyclic nucleotides cAMP and cGMP in bronchoalveolar lavage (BAL) fluids. Results in the six sheep with chronic allergic airway disease (reactive sheep) were compared to those of three sheep chronically exposed to antigen but without acute or chronic airway response (nonreactive sheep). Histamine levels in BAL fluids were not modified after antigen exposure in reactive and nonreactive groups. Before acute challenge, cAMP in BAL was 10.4 +/- 1.0 pmol/ml in reactive sheep and 16.4 +/- 1.0 in nonreactive sheep; cGMP was 0.16 +/- 0.01 pmol/ml in reactive sheep and 0.18 +/- 0.06 in nonreactive sheep. Antigen exposure did not change the lung lavage levels of cAMP or cGMP for up to 7 h in the nonreactive sheep. In the reactive sheep, antigen exposure induced a significant gradual fall in cAMP to 49% of the preexposure level and a rapid and sustained increase of cGMP to 200% of the preexposure level (P less than 0.05). Prechallenge lung resistance was increased in reactive sheep compared to nonreactive sheep. Antigen challenge further increased lung resistance in reactive sheep during the first hour without any change in nonreactive sheep. Reactive sheep BAL eosinophils increased to 900% of the values of nonreactive sheep at 4 and 7 h following challenge. These observations suggest that histamine does not have a major role in allergic response in the chronic sheep asthmatic model; furthermore, cyclic nucleotide modifications could reflect sympathoadrenergic imbalance and/or increase of inflammatory reaction following antigen exposure.(ABSTRACT TRUNCATED AT 250 WORDS)