Effects of 8-epi-PGF on isolated bronchial smooth muscle of healthy and heaves-affected horses

8-Epi-PGF, a prostaglandin-like compound generated by oxidative stress, has been shown to be an in vitro bronchoconstrictor in airways from healthy laboratory animals and healthy humans, but it has never been studied in diseased airways. Here, the bronchoconstrictive capacity of 8-epi-PGF on isolated bronchial rings (BR) of healthy and heaves-affected horses was evaluated by comparing the maximal effect and the potency of 8-epi-PGF to those of (1) acetylcholine (ACh), (2) its stereoisomer PGF and (3) its synthetic receptor agonist, U46619. Furthermore, the potential capacity of 8-epi-PGF to enhance the cholinergic (ACh) responsiveness of bronchial smooth muscle was investigated. 8-Epi-PGF contracted BR with a rank order of efficacy of Ach > U44619 > PGF > 8-epi-PGF in both healthy and heaves-affected horses. The contractile maximal response elicited by 8-epi-PGF was significantly smaller than that elicited by the other drugs, but was significantly higher in BR from heaves-affected horses than in those sampled in healthy horses, whilst pD values were similar. A subthreshold concentration of 8-epi-PGF (10 M) did not induce in vitro cholinergic hyper-responsiveness in BR of either healthy or heaves-affected horses. In conclusion, it has been demonstrated that 8-epi-PGF is an in vitro bronchoconstrictor of minor importance in healthy horses, but whose efficacy is significantly increased in heaves-affected horses.