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Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCβ2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.
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; La Fuente, José M 2 ; Sosa, Patricia 3 ; Fernández, Argentina 4 ; Pepe-Cardoso, Augusto J 5 ; Martínez-Salamanca, Juan I 6
; Rodríguez-Mañas, Leocadio 7
; Angulo, Javier 8
1 Fundación para la Investigación Biomédica del Hospital de Getafe, 28905 Getafe, Spain;
2 Serviço de Urologia, Centro Hospitalar e Universitário de Santo António (CHUdSA), 4099-001 Porto, Portugal;
3 Fundación para la Investigación Biomédica del Hospital de Getafe, 28905 Getafe, Spain;
4 Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología—IRYCIS/UFV, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain;
5 Serviço de Urologia, Hospital Fernando da Fonseca, 2720-276 Amadora, Portugal;
6 Servicio de Urología, Hospital Universitario Puerta de Hierro, 28222 Madrid, Spain;
7 Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain;
8 Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain;