title: 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.
authors.affiliation: Laboratory for Functional Investigation, Faculty of Veterinary Medicine, University of Liege, Sart Tilman, Belgium. Nathalie.Kirschvink@ulg.ac.be
authors.forename: N
authors.initials: N
authors.lastname: Kirschvink
authors.forename: F
authors.initials: F
authors.lastname: Bureau
authors.forename: T
authors.initials: T
authors.lastname: Art
authors.forename: P
authors.initials: P
authors.lastname: Lekeux
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016022:Case-Control Studies; D015237:Dinoprost / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D006734:Horse Diseases / Q000503:physiopathology*; D006736:Horses / Q000502:physiology*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology / Q000662:veterinary; D012130:Respiratory Hypersensitivity / Q000503:physiopathology / Q000662:veterinary*; D013928:Thromboxane A2 / Q000819:agonists; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
chemical_list: D000336:Aerosols; D016085:Bronchoconstrictor Agents; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost