EFFECT OF FENSPIRIDE ON PULMONARY-FUNCTION IN THE RAT AND GUINEA-PIG

1. Fenspiride is an anti-inflammatory agent that may have a role in re versible obstructive airways disease. Small, but significant, improvem ents have been seen in airways function and arterial oxygen tension in patients with mild chronic obstructive pulmonary disease. These chang es have been attributed to the anti-inflammatory properties of the dru g. However, airways function can be improved by other means, e.g. impr oved ventilation/perfusion ratio or reduced airways resistance. The po ssibility that fenspiride may have actions other than anti-inflammator y was investigated in two animal species. 2. In the rat, actions on th e pulmonary circulation were investigated in the isolated perfused lun g, but fenspiride proved to be a poor pulmonary vasodilator, showing o nly a small reversal of the raised pulmonary artery pressure induced b y hypoxia. 3. Ventilation was measured in the anaesthetized rat using whole-body plethysmography. Fenspiride caused no increase in ventilati on or changes in arterial blood gases. However, a profound hypotensive action was observed with high doses. 4. The possibility that a decrea se in airways resistance (R(aw)) might occur with fenspiride was inves tigated in anaesthetized guinea pigs. Capsaicin (30 mu mol/l was used to increase baseline R(aw) through bronchoconstriction. Fenspiride gav e a dose-dependent partial reversal of the raised R(aw), and its admin istration by aerosol proved as efficacious as the intravenous route. I n addition, the hypotensive side-effect found with intravenous injecti on was alleviated by aerosolized fenspiride. 5. An anti-bronchoconstri ctor action of fenspiride could be one of the mechanisms involved in i mproving airways function and PaO2, seen in mild chronic obstructive p ulmonary disease.