Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency.

Rommel Prata Regadas,Daniel Gabrielle Sucupira,Manoel Odorico De Moraes,Ricardo Reges,Lúcio Flávio Gonzaga-Silva,Francisco Vagnaldo F Jamacaru,João Batista Gadelha Cerqueira

doi:10.1590/s1677-5538.ibju.2014.04.15

Abstract

The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

Highlights

There is compelling evidence supporting a role for nitric oxide (NO)/cyclic guanosine monophosphate signaling pathways in the regulation of the micturition reflex (MR)
Tamsulosin/Tadalafil (n = 6): tamsulosin (1mg/kg/day) and tadalafil (5mg/kg/day) were given by oral gavage, and L-Nitroarginine methyl ester (L-NAME) diluted in the drink water; Based on dosages used in other studies, L-NAME (20mg/kg/ day) was administrated diluted in drinking water; tamsulosin (1mg/ kg /day) and tadalafil (5mg/kg/day) were administered by oral gavage for 30 days [14,15,16]
The administration of tadalafil decreased the non-voiding contractions (NVC) (0.66 ± 0.20), the amount of effect observed was not significant when compared with L-NAME Group

Summary

Introduction

There is compelling evidence supporting a role for nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathways in the regulation of the micturition reflex (MR). Proteins of the NO/cGMP signaling pathway have been identified in the human lower urinary tract (LUT), suggesting a potential role in the physiology of bladder [1,2]. The rationale for the use of PDE5i in the treatment of lower urinary tract symptoms (LUTS) was based on demographic data showing the frequent occurrence of both erectile dysfunction (ED) and LUTS in men as they age [9]. As a consequence of these population studies, high level of evidence studies have emerged that clearly shows improvement in LUTS after treatment with PDE5i [11,12,13]. Only few experimental studies have assessed the effect of this combination in the lower urinary tract

Objectives

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Results