Prolonged hyperglycemia decreased the adverse respiratory effects of benzodiazepines in rats

Introduction: The incidence of diabetes is increasing along with its associated respiratory disorders, sleep disturbance and mental health problems. Despite the adverse effects of benzodiazepine receptor agonists (BZRAs) on the respiratory system function, they remain the most commonly used medications for the management of anxiety and sleep disorders. The aim of this study was to investigate whether chronic hyperglycemia increases the adverse respiratory effects of BZRAs. Methods: The experiments were carried out in male Wistar rats that were randomly allocated into six experimental groups. Hyperglycemia was induced by injecting 35mg/kg streptozotocin (STZ). We recorded breathing of conscious animals using whole-body plethysmography at the onset of the experiment and three weeks after diabetes induction. Animals were subjected to intraperitoneal injection of midazolam (0.75mg/kg) and diazepam (1mg/kg) 15min prior to the second respiratory recording. Results: Analysis of respiratory dynamics revealed an alteration in breathing pattern in intact animals following the anxiolytic dose of benzodiazepines, which was associated with an increase in respiration rate and variability and decrease in the irregularity of the respiratory rhythm. Meanwhile, these effects were significantly decreased in hyperglycemic animals. Conclusion: Our results demonstrate that STZ-induced hyperglycemic rats exhibited decreased adverse respiratory effects of BZRAs. It seems that hyperglycemia induced an impairment in benzodiazepine receptors response to the BZRAs.