Thor Pj

The influence of melatonin and agomelatine on urodynamic parameters in experimental overactive bladder model--preliminary results.

INTRODUCTION Overactive bladder (OAB) is a common disease entity with complex pathogenesis that involves neurogenic, myogenic and abnormal paracrine urothelial activity mechanisms. Our objective was to estimate bladder functioning in urodynamic studies in experimental, both acute (AOAB) and chronic (COAB) cyclophosphamide (CYP)-evoked OAB model in response to melatonin (MLT; antioxidant and MT receptor agonist) or agomelatine (AMT; MT receptor agonist and 5HT2C receptor antagonist). MATERIAL/METHODS Seven groups were studied: 1--control, 2-4--MLT treated AOAB and COAB rats, 5-7--AMT treated AOAB and COAB rats. AOAB model was evoked by single CYP administration (IP 200 mg/kg body weight), while COAB one was induced by a four-time administration of CYP (IP 75 mg/kg body weight). Each group underwent urethane anesthesia to perform urodynamic recordings in resting conditions and after administration 50 (group 2 or 5), 75 (group 3 or 6) or 100 mg/kg (group 4 or 7) of melatonin (groups 2-4) or agomelatine (groups 5-7), followed by classical urodynamic parameters assessment. RESULTS Neither melatonin nor agomelatine did not affect urodynamic parameters in the AOAB rats. In COAB model, after 75 and 100 mg/kg of MLT we revealed an improvement in urodynamic parameters. AMT (75 and 100 mg/kg) administration caused deterioration of urodynamic findings suggesting bladder overactivity exacerbation. DISSCUSSION: In summary, melatonin ameliorates bladder overactivity in cyclophosphamide-induced COAB. Agomelatine, contrary to melatonin, aggravates bladder dysfunction in this group. These findings suggest that the improvement in urodynamic parameters after melatonin administration may be due to its antioxidative profile and is not related to MT receptors activation. However, agomelatines unfavorable action on the bladder, resulting in its overactivity in COAB group, may not only be the result of MT receptor activation without the concomitant antioxidative effects but may also occur secondarily to co-existing 5HT2C receptor antagonism.

Urine uromodulin estimation in partial bladder outlet obstruction and cyclophosphamide-induced haemorrhagic cystitis models in rats.

INTRODUCTION Uromodulin (UMOD) is a glycoprotein excreted by the thick ascending limb of the Henles loop and distal convoluted tubule cells, playing various, yet still unclear roles. An abnormal urinary UMOD excretion is observed in many pathophysiological conditions. The aim of our study was to assess urine UMOD excretion in experimental partial bladder outlet obstruction (PBOO), reflecting BPH in humans, and in cyclophosphamide-induced haemorrhagic cystitis (CP-HC). MATERIALS AND METHODS PBOO and CP-HC rats and two appropriate control groups were studied. The PBOO model was surgically induced by partial proximal urethral obstruction and CP-HC by four i.p. cyclophosphamide administrations (every two days). 24-hour urine collections were performed in both PBOO (on 3rd, 7th, 12th and 15th day after surgery) and CP-HC rats (on 1st, 3rd, 5th and 7th day). UMOD was determined with the ELISA method. Both 24-hour urinary UMOD excretion and urinary UMOD concentrations were determined. RESULTS In the overall assessment, PBOO rats were characterized by decreased mean urinary UMOD concentration. However, as the urine volume, except for transient drop on 3rd day following PBOO operation, was steadily increasing, the daily urinary uromodulin excretion did not differ from the control one. Contrary to PBOO, CP-HC rats demonstrated mean urinary concentration similar to that of the control rats, while their 24hr UMOD excretion in urine was almost doubled due to urine volume increase (from 1.6 up to almost 3 fold). The highest UMOD urinary output was observed after the 3rd and 4th doses of cyclophosphamide. DISCUSSION A reduced urinary UMOD excretion in early PBOO phase may be considered as a marker of distal tubular cells damage due to incomplete bladder emptying and increased pressure retrograding to distal tubules. This effect disappears with structural, adaptive histological changes of the bladder wall leading to an improved voiding. In CP-HC animals, the elevated urinary UMOD level may be associated with complex inflammatory response due to the cytotoxic CP action. UMOD assessment in this model may reflect renal and urological toxicity as UMOD excretion rises with the cumulative cyclophosphamide dose.

Heart rate variability after BRL37344, a beta-3 agonist, in experimental bladder outlet obstruction.

INTRODUCTION Bladder overactivity symptoms accompany benign prostatic hyperplasia (BPH) syndrome. The autonomic nervous system (ANS) disturbances may be involved in bladder dysfunction. An ameliorating effect on bladder overactivity is being assigned to the currently investigated β-3 adrenoreceptor agonists. However, little is known about the influence of β-3 agonists on ANS activity. The aim of our study was to estimate ANS activity using heart rate variability (HRV) in experimental model of bladder outlet obstruction (BOO), reflecting human BPH. MATERIAL/METHODS 30 female rats, divided into control, non-treated BOO (LLBOO), and β-3 agonist (BRL37344) BOO treated (LLBOO+β3 agonist) were studied. BOO was evoked by 5-week long partial proximal urethra ligation. Next, 20-minute resting HRV recordings were performed in each of the studied groups following i.p. administration of the vehicle (LLBOO) or BRL37344 (LLBOO+β3 agonist). RESULTS LLBOO rats were characterized by diminished NN range, SDNN, and rMSSD in time-domain analysis. Similarly, TP and non-normalized spectral HRV parameters were also decreased. Contrary to these findings, normalized spectral parameters were lower (nLF) and higher (nHF). The animals treated with BRL37344 demonstrated no significant differences in time--domain HRV parameters. In spectral analysis, a decrease in LF and HF, together with a fall in TP, was found. Moreover, both nLF and nHF reached almost the same values in control and β-3 agonist treated rats. DISSCUSSION: Our data indicates that BRL37344 is an agent abolishing the autonomic imbalance in experimental BOO, which may contribute to relieving the symptoms of bladder overactivity in β-3 agonists treated participants.