EFFECTS OF THE CALCIUM IONOPHORE A23187 ON AIRWAY RESPONSIVENESS TO HISTAMINE AND SUBSTANCE-P IN GUINEA-PIGS

Objective: We evaluated the mechanism of the airway hyperresponsivenes s (AHR) induced by a calcium ionophore in guinea pigs. Materials and M ethods: Airway responsiveness to intravenous histamine (HS) and substa nce P (SP) was measured 24 h after a 1-h exposure to aerosolized A2318 7 (0.03 or 0.1 mg/ml) or its vehicle (10% DMSO). Changes were assessed by calculating -logPC(350)HS and -logPC(350)SP. Neutral endopeptidase (NEP) activity in the airway tissues, as well as the nitrite (NO2-) l evels and the cell population in bronchoalveolar lavage fluid (BALF) w as determined after measurement of pulmonary function. Changes in SP-i nduced vascular permeability 24 h after exposure to A23187 were measur ed by the Evans Blue dye extravasation technique.Results: Exposure to A23187 caused a significant AHR to SP, along with a significant increa se in the number of neutrophils and epithelial cells in the BALF. Whil e there was no significant change in NEP activity in the airway tissue s, the levels of nitrite in the BALF were significantly decreased in A 23187-exposed animals. Significant correlations were found between the number of epithelial cells in the BALF and -logPC(350)SP (r = 0.477, p < 0.05) and between nitrite levels in the BALF and -logPC(350)SP (r = -0.491, p < 0.05). A23187 exposure did not significantly change the SP-induced airway microvascular leakage. Conclusions: These data sugge st that A23187 exposure induced AHR to SP possibly by reducing NO leve ls in the airway tissues. This may be due to damaged airway epithelium and/or NO breakdown by activated inflammatory cells in the airways of these guinea pigs.