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Nebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum and penile arteries from diabetic patients by enhancing the NO/cGMP pathway.

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dc.contributor.authorMartínez-Salamanca, J
dc.contributor.authorLa Fuente, J
dc.contributor.authorCardoso, J
dc.contributor.authorFernández, A
dc.contributor.authorCuevas, P
dc.contributor.authorWright, H
dc.contributor.authorAngulo, J
dc.date.accessioned2016-11-15T17:00:13Z
dc.date.available2016-11-15T17:00:13Z
dc.date.issued2014
dc.description.abstractINTRODUCTION: The efficacy of oral pharmacotherapy for erectile dysfunction (ED) (i.e., type 5 phosphodiesterase[PDE5] inhibitors) is significantly reduced in diabetic patients. Nebivolol is a selective β1-blocker used for treatinghy pertension that has been shown to increase the efficacy of sildenafil to reverse ED in diabetic rats. AIM: To evaluate the effects of nebivolol on the efficacy of the PDE5 inhibitors, sildenafil, tadalafil, and vardenafil to relax human corpus cavernosum (HCC) and vasodilate human penile resistance arteries (HPRA) from diabetic patients with ED (DMED). The influence of nebivolol on the capacity of these three PDE5 inhibitors to stimulate cyclic guanosine monophosphate (cGMP) production in HCC was also evaluated. METHODS: HCC and HPRA were obtained from organ donors without ED (NEND; n = 18) or patients with diabetes undergoing penile prosthesis implantation (DMED; n = 19). Relaxations of HCC strips and HPRA to sildenafil,tadalafil, and vardenafil were evaluated in organ chambers and wire myographs. cGMP content in HCC was determined by ether extraction and quantification by ELISA. MAIN OUTCOME MEASURES: Effects of nebivolol on PDE5 inhibitor-induced relaxation of HCC, vasodilation ofHPRA and cGMP accumulation in HCC. RESULTS: Treatment with nebivolol (1 μM) significantly potentiated sildenafil-, tadalafil- and vardenafil-induced relaxations of HCC and vasodilations of HPRA from both NEND and DMED. Enhancement of relaxant capacity by nebivolol resulted in reversion of the impairment of PDE5 inhibition-induced responses in DMED and it was accompanied by enhancing the ability of PDE5 inhibitors to increase cGMP in HCC restoring reduced cGMP levelsin HCC from DMED. CONCLUSIONS: Nebivolol potentiated the capacity of PDE5 inhibitors to relax vascular structures of erectile tissue from diabetic patients by enhancing the nitric oxide (NO)/cGMP pathway in these tissues. These effects suggest a potential therapeutic utility of nebivolol as an adjunct to PDE5 inhibitors for the treatment of ED associated with diabetes.pt_PT
dc.identifier.citationJ Sex Med. 2014 May;11(5):1182-92.pt_PT
dc.identifier.issn1743-6109
dc.identifier.urihttp://hdl.handle.net/10400.10/1750
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.subjectDiabetes mellitus type 2pt_PT
dc.subjectErectile dysfunctionpt_PT
dc.subjectDiabetes mellitus tipo 2pt_PT
dc.subjectDisfunção eréctilpt_PT
dc.titleNebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum and penile arteries from diabetic patients by enhancing the NO/cGMP pathway.pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1192pt_PT
oaire.citation.startPage1182pt_PT
oaire.citation.titleThe journal of sexual medicinept_PT
oaire.citation.volume11pt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT

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