DIETARY SALT CONSUMPTION AND LEUKOTRIENE-DEPENDENT HYPERPNEA-INDUCED AIRWAY OBSTRUCTION IN GUINEA PIGS

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The purpose of this study was to determine if altering dietary salt consumption moderates hyperpnea-induced airway obstruction (HIAO) in guinea pigs (an animal model of exercise-induced asthma), and to determine whether blocking leukotriene (LT) biosynthesis alters the airway response to hyperpnea on the different salt diets. Thirty-two male Hartley strain guinea pigs were split into two groups. One group (n = 16) of animals ingested a normal salt diet (NSD) for 2 weeks, while the other group (n = 16) ingested a high salt diet (HSD) for two weeks. Thereafter, animals were anesthetized, cannulated, tracheotomized, and mechanically ventilated during a baseline period and during a dry gas hyperpnea challenge. After the hyperpnea challenge, baseline ventilator settings were resumed and animals were administered either saline [NSD- CON (n = 8) and HSD-CON (n = 8)], or NDGA, a LT inhibitor [NSD-BLO (n = 8) and HSD-BLO (n = 8)]. Subsequently, a second hyperpnea challenge was followed by a second post-hyperpnea recovery period. Airway inspiratory pressures (Ptr) were monitored continiously Bladder urine was collected by needle aspiration after euthanasia, and analyzed for urinary concentrations of sodium, chloride, potassium and creatinine. There were no significant differences between the NSD and HSD diet for Ptr prior to the first hyperpnea challenge (p > 0.05). However, the HSD elicited higher Ptr than the NSD (p < 0.001) post-challenge. Following infusion of saline (CON), and a second hyperpnea challenge, the HSD-CON group demonstrated higher Ptr than the NSD diet group (p < 0.001). However, following infusion of the LT-inhibitor, and a second hyperpnea challenge, HIAO was attenuated in both the NSD-BLO and HSD-BLO groups compared to the CON groups respectively (p < 0.001). Nonetheless, the HSD-BLO group continued to demonstrate higher Ptr than the NSD-BLO group (p < 0.05). Conclusion: This study has demonstrated that dietary salt loading exacerbates the development of HIAO in guinea pigs, and that LT release is involved in HIAO and may be moderated by changes in dietary salt loading. (Supported by the College Research Council, College of Veterinary Medicine and Biomedical Sciences, Colorado State University)