Regional variability in the response of collateral resistance to histamine in the dog: effects of cyclooxygenase inhibition

Abstract

The aim of the study was to examine the role of cyclooxygenase metabolites in determining the variability in histamine responsiveness of the collateral channels of different lung segments of the dog. Using the wedged bronchoscope technique we measured the change in collateral resistance (Rcoll) to aerosolized histamine in two different lung segments of 5 anaesthetized, paralyzed, intubated, mongrel dogs. The same lung segments were examined twice under baseline conditions, and twice after indomethacin (INDO) pretreatment. Rcoll measurements were obtained under control conditions, after saline aerosol, and then after increasing concentration of histamine (range 0.1 μg/ml–10.0 mg/ml) were ultrasonically nebulized into the wedged segment. The concentration of histamine that elicited a 50% increase in Rcoll was calculated by log linear interpolation. In addition we performed bronchoalveolar lavage (BAL) in the wedged segment at the completion of the concentration-response curves, and assayed the BAL fluid for TXB2, PGE2, and 6-oxo-PGF1α. The geometric mean ratio of histamine responsiveness between lung segments of each animal was 42.5-fold under control conditions and fell to 9.1-fold after INDO (P<0.05). While the concentration of TXB2 fell in the BAL after INDO, concentrations of PGE2 and 6-oxo-PGF1α did not. Moreover, there was no correlation between levels of prostanoids and either responsiveness or variability in responsiveness of the collateral channels. Hence while cyclooxygenase blockade altered the regional variability in histamine responsiveness in the collateral channels, this change was not reflected in the levels of prostanoids in the BAL fluid.