Role of L‐Citrulline/L‐Arginine Cycle in Hyperoxia‐Induced Decrease of Airway Smooth Muscle Relaxation

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It was shown that inhibitory nonadrenergic noncholinergic (iNANC) nerve–induced nitric oxide (NO) production and airway smooth muscle (ASM) relaxation are impared after exposure to hyperoxia due to decrease of L‐arginine bioavailability to NO synthase (NOS). Therefore, we tested the hypothesis that L‐citrulline/L‐arginine cycle is active in rat pup airways and supplementation of tissues with L‐citrulline, restores impaired relaxation of ASM after exposure to hyperoxia. Tracheal rings were excised from rat pups 12 days old, exposed to hyperoxia or room air for seven days. In precontracted tracheal smooth muscle (TSM), electrical field stimulation (EFS) was applied to induce relaxation. In hyperoxic group, relaxation was reduced as compare to control group. Incubation of tissues with NOS inhibitor (L‐NAME), reduced relaxant responses in control group. In vitro supplementation of tissues with L‐citrulline reversed EFS‐induced relaxation of TSM of hyperoxic group at control level, but did not have any effect in control group under basal condition. Inhibition of enzymes involved in L‐citrulline recycling, prevented this effect of L‐citrulline.The data demonstrate that L‐citrulline/L‐arginine cycle is active in rat pup TSM and is effective under conditions of reduced bioavailability of L‐arginine to NOS. Presence of L‐citrulline restores hyperoxia‐induced decrease of ASM relaxation.