Inhibition of endothelin‐induced response on equine bronchial rings

Abstract

Airway hyperreactivity is the hallmark of human asthma and recurrent airway obstruction (RAO) in horses. Endothelin‐1 (ET‐1) is an inflammatory mediator that causes potent constriction of human and equine airways. Nuclear Factor‐kB (NF‐kB), a transcription factor, and Tumor Necrosis Factor‐alpha (TNFα), a cytokine, are well established molecules that are involved in inflammation. The objective of the study was to determine the effectiveness of Ammonium pyrrolidinedithiocarbamate (PDTC) and Pentoxifylline, antagonists of NFkB and TNFα respectively, on ET‐1 induced response of equine bronchial rings from RAO‐affected and unaffected horses. Rings from the 4th – 7th generation branches of airways were set in organ baths bubbled with O2 and filled with Tyrode's solution at 37°C. One side of the ring was fixed to the floor of the bath and the other end was connected to a force transducer interfaced with a polygraph. After application of two grams of tension and an equilibration period of 45 minutes, the response of the tissues to graded concentrations of ET‐1 was measured in one ring (control), one incubated with PDTC and another with Pentoxifylline. The results indicated that Pentoxifylline substantially inhibited the response caused by ET‐1 whereas, PDTC did not. These results suggested that TNFα may be involved in the contractile effects of ET‐1 in the equine airways with recurrent airway obstruction. Supported by Equine Health Studies Program of LSU School of Veterinary Medicine.