The Ameliorating Effect of Exogenous Melatonin on Urinary Bladder Function in Hyperosmolar Bladder Overactivity and its Influence on the Autonomic Nervous System Activity

Abstract

The pathophysiology of overactive bladder (OAB) is multifactorial. Although, the two pivotal myogenic (alterations in bladder smooth muscle contractility and excitability) and neurogenic (increased or sensitized sensory transmission, abnormalities in spinal and supraspinal control) basis for the OAB development have been proposed (4,8,28). The neurogenic theory explains that the backgrounds for OAB seems to be partially related to alterations in bladder afferent nerve fibres localized within the bladder mucosa.Animal studies revealed that the bladder mucosa is characterized by a significantly lower concentration of highenergy phosphates and higher oxidative metabolic rate than the detrusor smooth muscle. This facts point that the bladder mucosa is significantly more sensitive to anoxia than is the bladder smooth muscle (13,18). Azadzoi et al. (2) study revealed that long-term arterial insufficiency leads to bladder neuropathy via ischemia, hypoxia and oxidative stress. OAB under the ischemic condition generates neurotoxic oxidative and nitrosative products. Neurodegeneration is postulated to be an end stage phenomenon in ischemia induced bladder overactivity. The increased sensitivity of urothelium to different stimuli (e.g. hypoxia, ischemia, hyperosmotic agents, etc.) would indicate that bladder afferents (pain, altered sensations, reflex contractions) might be activated at levels of hypoxia/ischemia that have no direct effect on bladder smooth muscle function.Therefore, a novel strategies for therapeutic approach of OAB based on: 1) reducing the phasic increase in intracellular calcium that causes the activation of calcium activated hydrolytic enzymes, 2) stabilizing the neuronal or smooth muscle membrane components that are hydrolyzed by the activated enzymes; or 3) employing free radical scavengers that reduce the activation of cellular lipid peroxidases and the reperfusion injury, seem to be crucial (19 Summary: This study was designed to investigate the effects of melatonin on the bladder hyperactivity in hyperosmolar-induced overactive bladder (OAB) rats. Additionally, the influence of melatonin on the autonomic nervous system (ANS) using heart rate variability (HRV) analysis was assessed. 40 rats were divided into four groups: I -control (n=12), II -rats with hyperosmolar OAB (n=6), III -rats with melatonin pretreatment and hyperosmolar OAB (n=6) and IV -control with melatonin pretreatment (n=6). In group III and IV melatonin in dose of 100 mg/kg was given. HRV measurements in 10 rats, as follow: control (n=2), control after melatonin treatment (n=2), rats with hyperosmolar OAB without (n=3), and after (n=3) melatonin treatment were conducted. This study demonstrates marked influence of melatonin on urinary bladder activity in hyperosmolar-induced OAB rats. These rats showed significantly reduced the detrusor motor overactivity resulting in the improvement of cystometric parameters after melatonin treatment when compared to the control, as follow: a significant increase of intercontraction interval (70 ...

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