Effects of 8-epi-PGF(2 alpha) on isolated bronchial smooth muscle of healthy and heaves-affected horses

8-Epi-PGF(2 alpha), a prostaglandin-like compound generated by oxidative st ress, has been shown to be an in vitro bronchoconstrictor in airways from h ealthy laboratory animals and healthy humans, but it has never been studied in diseased airways, Here, the bronchoconstrictive capacity of 8-epi-PGF(2 alpha) on isolated bronchial rings (BR) of healthy and heaves-affected hor ses was evaluated by comparing the maximal effect and the potency of 8-epi- PGF(2 alpha) to those of (1) acetylcholine (ACh), (2) its stereoisomer PGF( 2 alpha) and (3) its synthetic receptor agonist, U46619. Furthermore, the p otential capacity of 8-epi-PGF(2 alpha) to enhance the cholinergic (ACh) re sponsiveness of bronchial smooth muscle was investigated, 8-Epi-FGF(2 alpha ) contracted BR with a rank order of efficacy of Ach > U44619 > PGF(2 alpha ) > 8-epi-PGF(2 alpha) in both healthy and heaves-affected horses. The cont ractile maximal response elicited by 8-epi-PGF(2 alpha) was significantly s maller 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(2) values were similar. A subthreshold concentration of 8-epi-PGF (2 alpha) (10(-7) M) did not induce in vitro cholinergic hyper-responsivene ss in BR of either healthy or heaves-affected horses, In conclusion, it has been demonstrated that 8-epi-PGF(2 alpha) is an in vitro bronchoconstricto r of minor importance in healthy horses, but whose efficacy is significantl y increased in heaves-affected horses.