Signalling pathways involved in sildenafil‐induced relaxation of human bladder dome smooth muscle

Background and purpose:  The mechanism(s) of action responsible for the beneficial effects of phosphodiesterase 5 (PDE5) inhibitors including sildenafil on lower urinary tract symptoms suggestive of benign prostate hyperplasia are unclear. In particular, the role of the NO‐cGMP signalling pathway in regulating human bladder dome smooth muscle relaxation is questionable. Thus, we assessed the ability of a PDE5 inhibitor, sildenafil, to relax such tissue, and identified the signalling pathways involved in this relaxation.

[1]  H. Uemura,et al.  Chronic treatment with a PDE5 inhibitor increases contractile force of normal bladder in rats , 2010, International Urology and Nephrology.

[2]  K. Andersson,et al.  Vardenafil‐induced relaxation and cyclic nucleotide levels in normal and obstructed rat urinary bladder , 2009, BJU international.

[3]  M. Carini,et al.  Vardenafil modulates bladder contractility through cGMP-mediated inhibition of RhoA/Rho kinase signaling pathway in spontaneously hypertensive rats. , 2009, The journal of sexual medicine.

[4]  T. Lebret,et al.  Combination of doxazosin and sildenafil exerts an additive relaxing effect compared with each compound alone on human cavernosal and prostatic tissue. , 2009, The journal of sexual medicine.

[5]  C. Roehrborn,et al.  Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. , 2008, The Journal of urology.

[6]  C. Roehrborn,et al.  Lower urinary tract symptoms revisited: a broader clinical perspective. , 2008, European urology.

[7]  C. Stief,et al.  A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. , 2008, European urology.

[8]  F. Giuliano.  Phosphodiesterase type 5 inhibitors improve male lower urinary tract symptoms. , 2008, European urology.

[9]  K. Kohri,et al.  Role of nitric oxide/cyclic GMP pathway in regulating spontaneous excitations in detrusor smooth muscle of the guinea‐pig bladder , 2008, Neurourology and urodynamics.

[10]  S. Oger,et al.  PDE5 GENE EXPRESSION AND RELAXANT EFFECTS OF VARDENAFIL IN MALE AND FEMALE HUMAN AND RAT DETRUSOR MUSCLE , 2008 .

[11]  J A Peters,et al.  Guide to Receptors and Channels (GRAC), 3rd edition , 2008, British journal of pharmacology.

[12]  R. B. de Oliveira,et al.  Sildenafil inhibits duodenal contractility via activation of the NO–K+ channel pathway , 2008, Fundamental & clinical pharmacology.

[13]  J. Medeiros,et al.  Role of the NO/cGMP/KATP pathway in the protective effects of sildenafil against ethanol‐induced gastric damage in rats , 2008, British journal of pharmacology.

[14]  C. Roehrborn,et al.  Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. , 2007, The Journal of urology.

[15]  M. Carini,et al.  Vardenafil improves urodynamic parameters in men with spinal cord injury: results from a single dose, pilot study. , 2007, The Journal of urology.

[16]  M. Carini,et al.  Characterization and functional role of androgen-dependent PDE5 activity in the bladder. , 2007, Endocrinology.

[17]  T. Lebret,et al.  Relaxation of phasic contractile activity of human detrusor strips by cyclic nucleotide phosphodiesterase type 4 inhibition. , 2007, European urology.

[18]  K. McVary,et al.  Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. , 2007, The Journal of urology.

[19]  P. Sandner,et al.  Pre‐clinical evidence for the use of phosphodiesterase‐5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms , 2006, BJU international.

[20]  L. Rivera,et al.  Role of nitric oxide in the relaxation elicited by sildenafil in penile resistance arteries. , 2006, The Journal of urology.

[21]  N. Villalba,et al.  Ca2+-activated K+ (KCa) channels are involved in the relaxations elicited by sildenafil in penile resistance arteries. , 2006, European journal of pharmacology.

[22]  G. Christ,et al.  Molecular mechanisms of detrusor and corporal myocyte contraction: identifying targets for pharmacotherapy of bladder and erectile dysfunction , 2006, British journal of pharmacology.

[23]  P. Hedlund.  Nitric oxide/cGMP-mediated effects in the outflow region of the lower urinary tract—is there a basis for pharmacological targeting of cGMP? , 2005, World Journal of Urology.

[24]  S. Archer,et al.  The neurovascular mechanism of clitoral erection: nitric oxide and cGMP‐stimulated activation of BKCa channels , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  J. Corbin,et al.  Mechanisms of action of PDE5 inhibition in erectile dysfunction , 2004, International Journal of Impotence Research.

[26]  E. Bischoff.  Potency, selectivity, and consequences of nonselectivity of PDE inhibition , 2004, International Journal of Impotence Research.

[27]  P. Boyle,et al.  [Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging.male (MSAM-7)]. , 2003, Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie.

[28]  C. Stief,et al.  Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle , 1996, Urological Research.

[29]  J. Reynard,et al.  Nitric oxide and the lower urinary tract: current concepts, future prospects. , 2003, Urology.

[30]  H. Kilbinger,et al.  Inhibition of human detrusor contraction by a urothelium derived factor. , 2003, The Journal of urology.

[31]  S. Hourani,et al.  Sodium nitroprusside-induced rat fundus relaxation is ryanodine-sensitive and involves L-type Ca2+ channel and small conductance Ca(2+)-sensitive K+ channel components. , 2002, Autonomic & autacoid pharmacology.

[32]  D. Webb,et al.  Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. , 2002, Urology.

[33]  A. Moon.  Influence of nitric oxide signalling pathways on pre‐contracted human detrusor smooth muscle in vitro , 2002, BJU international.

[34]  S. Lee,et al.  Effects of nitric oxide on the Ca2+-activated potassium channels in smooth muscle cells of the human corpus cavernosum , 2001, Urological Research.

[35]  C. Stief,et al.  Initial clinical experience with the selective phosphodiesterase-I isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder , 2000, World Journal of Urology.

[36]  U. Jonas,et al.  Effects of sildenafil on cAMP and cGMP levels in isolated human cavernous and cardiac tissue. , 2000, Urology.

[37]  G. Angelini,et al.  Prostaglandins and cyclic nucleotides in the urinary bladder of a rabbit model of partial bladder outlet obstruction. , 1999, Prostaglandins, leukotrienes, and essential fatty acids.

[38]  A. Kanai,et al.  Adrenergic- and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. , 1998, American journal of physiology. Renal physiology.

[39]  C. Stief,et al.  Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. I. Identification and characterization. , 1998, Urological research.

[40]  K. Andersson,et al.  Nitric oxide and relaxation of pig lower urinary tract , 1992, British journal of pharmacology.

[41]  R. Paoletti,et al.  Prostaglandins and Cyclic Nucleotides , 1982 .