Effects of Combination Treatment of Alpha 1-Adrenergic Receptor Antagonists on Voiding Dysfunction: Study on Target Organs in Overactive Bladder Rats

Abstract

PurposeOveractive bladder (OAB) causes urinary urgency, usually accompanied by frequency and nocturia. Alpha 1-adrenergic receptor (α1-AR) antagonists are known to improve lower urinary tract symptoms associated with OAB. The α1-AR antagonists constitute a variety of drugs according to the receptor subtype affinity. This study investigated the efficacy of tamsulosin, naftopidil, and a combination of the two on OAB rats.MethodsThe OAB rat model was induced by an intraperitoneal injection of cyclophosphamide for 14 days. The experimental groups were divided into 5 groups: control group, OAB-induction group, OAB-induction and tamsulosin monotherapy group, OAB-induction and naftopidil monotherapy group, and OAB-induction and tamsulosin-naftopidil combination therapy group. For the drug-treated groups, each drug was administrated for 14 days after the OAB induction. Cystometry for urodynamic evaluation and immunohistochemical stain for c-Fos and nerve growth factor (NGF) expressions in the central micturition centers were performed.ResultsIncreased contraction pressure and time with enhanced c-Fos and NGF expressions in the central micturition centers were found in the OAB rats. Tamsulosin suppressed contraction pressure and time while inhibiting c-Fos and NGF expressions. Naftopidil showed no significant effect and combination therapy showed less of an effect on contraction pressure and time. Naftopidil and combination therapy exerted no significant effect on the c-Fos and NGF expressions.ConclusionsTamsulosin showed the most prominent efficacy for the treatment of OAB compared to the naftopidil and combination. The combination of tamsulosin with naftopidil showed no synergistic effects on OAB; however, further studies of addon therapy might provide opportunities to find a new modality.

Add-on Therapy With the α-Blockers Tamsulosin and Naftopidil Improves Voiding Function by Enhancing Neuronal Activity in Prostatic Hyperplasia Rats

“…Both α1-AR subtype antagonists alleviate bladder outlet obstruction symptoms, such as residual urine and urinary urge sensation, by reducing the prostate size [ 18 ]. Overactive bladder symptoms, including frequency, urgency, nocturia, and urgency incontinence, were decreased by α1-AR antagonists in clinical and animal studies [ 12 , 19 ]. Furthermore, α1-AR antagonists increase bladder capacity and decrease frequency [ 10 , 20 ].…”

“…The animals were sacrificed immediately after evaluating their voiding function by cystometry, following a previously described method [ 10 , 12 ]. The rats were anesthetized using Zoletil 50 (10 mg/kg, interperitoneally; Virbac Laboratories), transcardially perfused with 50mM phosphate-buffered saline (PBS), and fixed with freshly prepared 4% paraformaldehyde in 100 mM phosphate buffer (pH, 7.4).…”

“…An immunohistochemical analysis was conducted to evaluate c-Fos and NGF expression in the MPA, vlPAG, PMC, and spinal cord L4–5 regions, following a previously described method [ 10 , 12 ]. Free-floating tissue sections were incubated overnight with rabbit anti-c-Fos and mouse anti-NGF antibodies (1:1,000; Santa Cruz Biotechnology, Santa Cruz, CA, USA) and the sections were incubated for 1 hour with biotinylated anti-rabbit c-Fos and anti-mouse NGF secondary antibodies (1:200; Vector Laboratories, Burlingame, CA, USA).…”

Low-frequency electroacupncture improves locomotor function after sciatic crushed nerve injury in rats

“…de Medeiros et al (2003) demonstrated the EA exerted analgesic effect and influenced c-Fos expression in the rats with peripheral neuropathic pain. Increased c-Fos expression represents peripheral nerve activation (Han et al, 2017; Ko et al, 2016).…”

“…For immunolabeling of c-Fos in the PVN and vlPAG, c-Fos immunohistochemistry was performed as the previously described method (Han et al, 2017; Ko et al, 2016). Free-floating tissue sections were incubated overnight with rabbit anti-c-Fos antibody (1:1,000; Santa Cruz Biotechnology, Santa Cruz, CA, USA), and the section were then incubated for 1 hr with biotinylated anti-rabbit secondary antibody (1:200; Vector Laboratories, Burlingame, CA, USA).…”