Bronchoconstrictive properties of inhaled 8-epi-PGF2alpha in healthy and heaves-susceptible horses

Abstract

The 8-epi-PGF2alpha is a marker of oxidative stress which is increased in lungs of asthmatic humans and heaves-susceptible horses. 8-Epi-PGF2alpha has also been demonstrated to be an in vitro and in vivo bronchoconstrictor in humans and rodents. We hypothesised that inhaled 8-epi-PGF2alpha was a bronchoconstrictor in healthy and heaves-susceptible horses in clinical remission. The effect on ventilatory mechanics of nebulised 8-epi-PGF2alpha was compared to that of PGF2alpha and U46619, a thromboxane A2 agonist. Pulmonary resistance (R(L)) and dynamic compliance (Cdyn) were assessed in six healthy horses and in six heaves-susceptible horses in clinical remission before (baseline) and immediately after a single inhalation challenge of 1 mg 8-epi-PGF2alpha PGF2alpha, or U46619 and placebo. R(L) and Cdyn were unchanged after inhalation of 8-epi-PGF2alpha in healthy horses. In heaves-susceptible horses, 8-epi-PGF2alpha induced a significant increase of R(L) and a significant decrease of Cdyn when compared to baseline values. Differences between R(L) and Cdyn values after 8-epi-PGF2alpha inhalation and those of placebo inhalation were not significant. Differences with healthy horses were not significant. PGF2alpha and U46619 induced a significant bronchoconstriction in healthy (R(L) and Cdyn versus baseline) and heaves-susceptible horses (R(L) and Cdyn, versus baseline and placebo), the R(L) increase in heaves-susceptible horses after PGF2alpha inhalation was significantly higher than that in healthy horses. Our results suggest that 8-epi-PGF2alpha is not a bronchoconstrictor in healthy horses, and a bronchoconstrictor far less efficient than PGF2alpha and U46619 at the same dose in heaves-susceptible horses.