Effects of Phosphodiesterase Inhibitors on Contraction Induced by Endothelin-1 of Isolated Human Prostatic Tissue

Kedia, George T.; Ückert, Stefan; Kedia, Merab; Kuczyk, Markus A.

doi:10.1016/j.urology.2008.11.041

Cited by 29 publications

(26 citation statements)

References 27 publications

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“…In human bladder neck samples, the rolipram relaxations were much stronger than those produced by the PDE5 blockers sildenafil and vardenafil. These results agree with those obtained in human prostate, where a high PDE4 expression, as well as a higher potency of rolipram in producing smooth muscle relaxation, in comparison with that elicited by PDE5 inhibitors, has been described [7,51]. This together with the fact that rolipram has previously been demonstrated to have no considerable effects on the systemic circulation in vivo [52] raises the possibility for the use of PDE4 inhibitors, alone or in combination with the PDE5 ones, for bladder outlet region smooth muscle relaxation.…”

Section: Discussionsupporting

confidence: 91%

Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck

Ribeiro¹,

Fernandes²,

Martínez‐Sáenz

et al. 2014

The Journal of Sexual Medicine

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Introduction Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility. Aim To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck. Methods Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension for rolipram in bladder neck samples were used. Main Outcome Measures PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension. Results PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram> > sildenafil>vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa) and intermediate (IKCa) conductance Ca2+-activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase. Conclusions PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]idesensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.

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Section: Discussionsupporting

confidence: 91%

Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck

Ribeiro¹,

Fernandes²,

Martínez‐Sáenz

et al. 2014

The Journal of Sexual Medicine

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“…FDA has approved tadalafil (5 mg) for LUTS with the objective to treat both the diseases simulataneouly and without worsening one of diseases. [10][11][12] PDE5 inhibitors acts by upregulation of the NO/cGMP activity. Preclinical studies reported partial reversal of nor-epinephrine-and endothelin-1-reduced prostatic tissue contraction 13 and an anti-proliferative effect on cultured prostate and bladder smooth muscle cells 14 .…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of Tadalafil and Tamsulosin as on therapy For Lower Urinary Tract Symptoms Due To Benign Hyperplasia of Prostate.

Pawar¹,

Kumar²,

Singh³

et al. 2016

IOSR

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“…Square-shaped strip preparations of isolated human prostate tissue were mounted to the chambers (volume 10 mL) of a vertical organ bath system (IOA 5306, F ö hr Medical Instruments GmbH, Seeheim, Germany) and maintained as has been described previously [ 20 ] . A pretension of 0.5 gr.…”

Section: Tissue Bath Studiesmentioning

confidence: 99%

Arginase enzymes in the human prostate: expression of arginase isoenzymes and effects of arginase inhibitors on isolated human prostate tissue

Kedia

Sonnenberg²,

Kuczyk

et al. 2012

BJU International

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Effects of Phosphodiesterase Inhibitors on Contraction Induced by Endothelin-1 of Isolated Human Prostatic Tissue

Cited by 29 publications

References 27 publications

Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck

Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck

Comparative Study of Tadalafil and Tamsulosin as on therapy For Lower Urinary Tract Symptoms Due To Benign Hyperplasia of Prostate.

Arginase enzymes in the human prostate: expression of arginase isoenzymes and effects of arginase inhibitors on isolated human prostate tissue

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