Under physiological conditions, hypochlorous acid (HOCl) is the major product of myeloperoxidase, a ferric heme enzyme released in inflammatory diseases. In the present study, we investigated the effect of HOCI compared to hydrogen peroxide (${H_2}{O_2}$) on the vasoactive intestinal polypeptide (VIP)-induced relaxation of feline lower esophageal sphincter (LES) strips. Isometric tension on LES strips was measured using a force transducer. VIP induced the relaxation of basal LES tone in a concentration-dependent manner. Pretreatment with HOCI ($10^{-4}M$) significantly reduced the VIP-induced relaxation at smaller concentrations than ${H_2}{O_2}$ ($10^{-3}M$). VIP-induced relaxation is mediated via the Gi/o protein, since pretreatment with Pertussis Toxin (PTX) showed an inhibitory effect on the relaxation. HOCl showed an additional inhibitory effect on the reduced relaxation by PTX, indicating that HOCl might affect another G protein as well as Gi/o. However, HOCl did not affect SNP-, SIN-1-, and 8-br-cGMP-induced relaxation. Nor did HOCl modify the relaxation induced by either forskolin or db-cAMP in LES muscle strips. These results suggest that during short-term treatment, HOCl may damage the upstream events including G protein level, and result in alteration of LES tone in the feline esophagus, similar to the inhibitory effects of ${H_2}{O_2}$.