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

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.

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).

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.