Effect of Fenspiride on Bronchial Smooth Muscle of Rats with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is among the leading causes of morbidity and mortality worldwide. Glucocorticoids are currently the most applicable anti-inflammatory treatment for COPD. However, a subset of COPD subjects is relatively insensitive to this treatment. Fenspiride, a non-corticosteroid anti-inflammatory drug, has been described to have beneficial effects in patients with COPD, although the mechanism of its action is not well known. The effect of fenspiride on contractile activity of bronchial smooth muscle was studied in a rat model of COPD induced by long-term exposure of the animals to nitrogen dioxide (NO(2)). Contractile activity of bronchial smooth muscle was evaluated in vitro. Isometric contraction of bronchial preparations was measured following electrical stimulation. Fenspiride administration to rats during the acute stage of COPD (15 days of NO(2) exposure) prevented the bronchial constriction induced by NO(2). The bronchodilator effect of a low-dose of fenspiride (0.15 mg/kg) was mediated by interaction with the nerve endings of capsaicin-sensitive C-fibers. Interaction of fenspiride with C-fibers was shown to prevent initiation of neurogenic inflammation, as evidenced by lack of COPD-like structural changes in the lungs. The bronchodilator effect of a high-dose of fenspiride (15 mg/kg) was mediated not only by the afferent component, but also involved a direct relaxing effect on smooth muscle cells. The anti-inflammatory and bronchodilator effects of a low-dose of fenspiride may be used for prevention of COPD development in individuals from high-risk cohorts exposed to aggressive environmental factors.