Tadalafil Enhances the Inhibitory Effects of Tamsulosin on Neurogenic Contractions of Human Prostate and Bladder Neck

• Published in: Journal of sexual medicine 2012-09, Vol.9 (9), p.2293-2306
• Main Authors: Angulo, Javier, Cuevas, Pedro, Fernández, Argentina, La Fuente, José M., Allona, Antonio, Moncada, Ignacio, Sáenz de Tejada, Iñigo
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-1 Receptor Antagonists - pharmacology; Benign Prostatic Hyperplasia; Carbolines - pharmacology; Electric Stimulation; Erectile Dysfunction; Humans; Lower Urinary Tract Symptoms; Male; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Nitric Oxide Donors - pharmacology; Nitroprusside - pharmacology; Phosphodiesterase 5 Inhibitors - pharmacology; Phosphodiesterase Type 5 Inhibitors; Prostate - physiopathology; Prostatic Hyperplasia - physiopathology; Sulfonamides - pharmacology; Tadalafil; Tamsulosin; Urinary Bladder - physiopathology
• ISSN: 1743-6095; 1743-6109
• DOI: 10.1111/j.1743-6109.2012.02821.x

Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH‐LUTSs) may be associated with erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors used for treating ED have shown clinical benefit in patients with LUTS but their actions in human LUT tissues are not well defined. To determine the effects of the long‐acting PDE5 inhibitor, tadalafil, on smooth muscle tone in human prostate and bladder neck as well as to evaluate the influence of tadalafil on the efficacy of the α‐adrenergic receptor antagonist, tamsulosin, in inhibiting contractile responses in these tissues. Strips of human peripheral prostate (HPP), human internal prostate (HIP), and human bladder neck (HBN) were obtained from organ donors and patients with BPH. The strips were then disposed in organ baths to evaluate nitric oxide/cyclic guanosine monophosphate (cGMP)‐mediated relaxation and cGMP kinetics in HPP and HIP, and electrical field stimulation (EFS)‐induced neurogenic contractions in HPP and HBN. Tadalafil‐induced effects on sodium nitroprusside (SNP)‐induced relaxation and cGMP accumulation in HPP and HIP and influence of tadalafil and tamsulosin on EFS‐induced contractions of HPP and HBN. SNP‐induced relaxation of HPP and HIP was significantly potentiated by tadalafil (30–60 nM). SNP‐induced cGMP accumulation in HPP and HIP was enhanced by tadalafil (30–60 nM), but significant difference was only obtained in HPP. EFS‐induced contractions sensitive to tetrodotoxin in HPP were significantly inhibited by tadalafil (30 nM) but not by tamsulosin (0.01–100 nM) or vehicle. Further inhibition of neurogenic responses in HPP was achieved by combining tadalafil and tamsulosin treatments. Tamsulosin, but not tadalafil, significantly reduced EFS‐induced contractions in HBN, but the coadministration of both therapies resulted in additional inhibition of contractions. While tadalafil enhances cGMP accumulation and potentiates prostate relaxation, tadalafil combined with tamsulosin results in enhanced inhibition of neurogenic contractions of HPP and HBN. Angulo J, Cuevas P, Fernández A, La Fuente JM, Allona A, Moncada I, and Sáenz de Tejada I. Tadalafil enhances the inhibitory effects of tamsulosin on neurogenic contractions of human prostate and bladder neck. J Sex Med 2012;9:2293–2306.