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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Mar 28

PMID 38542085

Authors

Mariam El Assar

Jose M La Fuente

Patricia Sosa

Argentina Fernandez

Augusto J Pepe-Cardoso

Juan I Martinez-Salamanca

Leocadio Rodriguez-Manas

Javier Angulo

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Targeting TRPC-5 Channel Inhibition to Improve Penile Vascular Function in Erectile Dysfunction.

El Assar M, Garcia-Gomez B, La Fuente J, Alonso-Isa M, Martinez-Salamanca J, Fernandez A Int J Mol Sci. 2025; 26(4).

PMID: 40003900 PMC: 11855833. DOI: 10.3390/ijms26041431.

Computational Investigation of the Therapeutic Potential of in the Management of Erectile Dysfunction.

Ejeje J, Agbebi E, Mathenjwa-Goqo M, Oje O, Agboinghale P, Ebe I Int J Mol Sci. 2024; 25(22).

PMID: 39596427 PMC: 11594949. DOI: 10.3390/ijms252212362.

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