Imagen de Portada

PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase

Guardado en:
Publicado en:International Journal of Molecular Sciences vol. 25, no. 6 (2024), p. 3111
Autor principal: Mariam El Assar
Otros Autores: La Fuente, José M, Sosa, Patricia, Fernández, Argentina, Pepe-Cardoso, Augusto J, Martínez-Salamanca, Juan I, Rodríguez-Mañas, Leocadio, Angulo, Javier
Publicado:
MDPI AG
Materias:
Endothelium
Veins & arteries
Diabetes
Penis
Kinases
Erectile dysfunction
Oxidative stress
Acceso en línea:Citation/Abstract
Full Text + Graphics
Full Text - PDF
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Resumen: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.
ISSN:1661-6596
1422-0067
DOI:10.3390/ijms25063111
Fuente:Health & Medical Collection