The complex pathogenesis of cyclophosphamide-induced hemorrhagic cystitis involves arachidonic acid-derived inflammatory mediators, among them leukotrienes. Montelukast, a leukotriene receptor antagonist, is reported to exert an alleviatory effect in the course of cystitis associated with overactive bladder symptoms. The aim of this study was to verify whether the effect of montelukast is also associated with its influence on autonomic activity. The experiment included 20 rats with cyclophosphamide-induced hemorrhagic cystitis (75 mg/kg, four doses every second day), among them, 10 treated with oral montelukast (10 mg/kg for 8 days) and 10 controls. Time and frequency domain analyses of heart rate variability (HRV) were conducted in all the rats as an indirect measure of their autonomic activity. The montelukast-treated animals showed an increase in root mean square of successive differences (rMSSD), as well as an increase in HRV spectrum total power (TP) and power of very low (VLF) spectral component. This suggests that due to its anti-inflammatory and its anti-leukotriene effect, montelukast improves overall autonomic activity, with no preferential influence on either the sympathetic or parasympathetic part. Furthermore, the increase in VLF corresponds to attenuation of inflammatory response. In conclusion, this study showed that aside from its antagonistic effect on leukotriene receptors, montelukast can also modulate autonomic activity.
Cyclophosphamide (CP) treatment is associated with the risk of haemorrhagic cystitis (HC). Moreover, CP-induced HC is complicated by autonomic nervous system (ANS) dysfunction. Pemirolast is thought to be a mast cell stabiliser that inhibits the release of many inflammatory mediators and sensory neuropeptides, and thus, it may be considered a potential chemoprotective HC agent. The aim of the study was to indirectly estimate the effect of pemirolast in experimental HC by measuring ANS activity with the heart rate variability (HRV) method. In CP-treated rats, we found a decreasing trend of overall autonomic activity, together with an imbalance between the main components, and a dominant very low frequency (VLF) power component. Pemirolast treatment did not improve the total HRV power value or the main non-normalized HRV components. Moreover, CP-HC animals treated with pemirolast displayed a different disproportion of normalized spectral components as compared to both control and CP-HC animals without pemirolast treatment, with the balance between normalized low frequency (nLF) and normalized high frequency (nHF) shifted towards nLF. This finding, together with a relatively high VLF tension, indicates that the pemirolast treatment resulted in high sympathetic activity that may contribute to HC exacerbation; thus, this agent seems to be ineffective in CP-induced HC.
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