RT Journal Article
T1 Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck
A1 Fernandes Ribeiro, Ana Sofía
A1 Fernandes, Vítor S.
A1 Martínez Sáenz, Ana
A1 Martínez Sainz, María Del Pilar
A1 Barahona Gomáriz, María Victoria
A1 Orensanz Muñoz, Luis Miguel
A1 Blaha, Igor
A1 Serrano Margüello, Daniel
A1 Bustamante, Salvador
A1 Carballido, Joaquín
A1 García Sacristán, Albino
A1 Prieto Ocejo, Dolores
A1 Hernández Rodríguez, Medardo Vicente
AB 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 (H2 S) 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+]i desensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.
PB Oxford University Press
SN 1743-6095
YR 2014
FD 2014-04-01
LK https://hdl.handle.net/20.500.14352/100452
UL https://hdl.handle.net/20.500.14352/100452
LA eng
NO Ribeiro ASF, Fernandes VS, Martínez-Sáenz A, Martínez P, Barahona MV, Orensanz LM, Blaha I, Serrano-Margüello D, Bustamante S, Carballido J, García-Sacristán A, Prieto D, Hernández M. Powerful relaxation of phosphodiesterase type 4 inhibitor rolipram in the pig and human bladder neck. J Sex Med. 2014 Apr;11(4):930-941. doi: 10.1111/jsm.12456. Epub 2014 Feb 12. PMID: 24754330.
DS Docta Complutense
RD 7 abr 2025