Early administration of phosphodiesterase 5 inhibitors after induction of diabetes in a rat model may prevent erectile dysfunction

Abstract

BackgroundThe possible role of phosphodiesterase 5 inhibitors (PDE5Is) in prevention of negative effect of diabetes mellitus (DM) on erectile function is not well settled.ObjectivesTo investigate the effect of early administration of vardenafil on erectile function, cavernosal structure, and genes expression in a rat model of DM.Materials and methodsThis experimental study was carried out at Suez Canal University's research laboratory. This study was conducted on a total of 60 adult male Albino Wistar rats, aged 60–80 days and weighing an average of 200 g. Rats were equally divided into six groups of 10 rats each: Group I (sham); Group II (DM with no treatment); Groups III, IV, V, and VI received vardenafil started at day 1, week 4, week 8, and week 12 after induction of DM, respectively. Functional study assessment of all groups was performed before euthanization, and then tissues were harvested for histopathological, ultrastructural, and molecular examinations.ResultsThere was a significant difference of intracavernosal pressure between early (94 ± 2.18) and late (40.5 ± 1.94) treatment groups (p = 0.011). Histopathological and ultrastructural changes of DM with no treatment and late treatment groups showed distorted cavernous architecture and extensive fibrosis. There was significant difference of smooth muscle to collagen ratio between early and late treatment groups (p = 0.035). There was significant upregulation of nNOS(p = 0.021) and iNOS (p = 0.047) in early vs. late treatment group. The difference was insignificant in eNOS (p = 0.386) or TGF‐β1(p = 0.149).Discussion and conclusionEarly treated rats with vardenafil had preserved erection and normal cavernosal structure, ultrastructure and gene expression of iNOS, nNOS, eNOS, and TGF‐β1. Quantification of gene expression would improve our knowledge regarding cytokines expression and molecular background of DM‐associated ED. Clinical application of this result may encourage early administration of PDE5I to prevent deleterious effects of DM on erectile function in newly diagnosed DM patients with probable uncontrolled blood glucose.

Single-cell transcriptome analysis of cavernous tissues reveals the key roles of pericytes in diabetic erectile dysfunction

“…Furthermore, we analyzed cell type-specific transcriptional changes due to diabetes ( Figure 1F and Figure 1—figure supplement 2A–G ). We found that Nos3 (highly expressed in the untreated diabetes group compared to the treatment group) decreased in diabetic valve-related LEC and VEC ( Ismail et al, 2020 ). In addition, Igfbp2 and Igfbp4 (lowly expressed in the penis of diabetic rats) were also downregulated in diabetic SMCs and Chonds, respectively, whereas Igfbp3 was upregulated in diabetic FB and MFB ( Abdelbaky et al, 1998 ).…”

Single cell transcriptome analysis of cavernous tissues reveals the key roles of pericytes in diabetic erectile dysfunction

“…2A-G). We found that Nos3 (highly expressed in the untreated diabetes group compared to the treatment group) decreased in diabetic valve-related LEC and VEC (Ismail et al, 2020). In addition, Igfbp2 and Igfbp4 (lowly expressed in the penis of diabetic rats) were also downregulated in diabetic SMC and chondrocytes, respectively, whereas Igfbp3 was upregulated in diabetic FB and Myo-FB (Abdelbaky et al, 1998).…”

X‐ray micro‐computed tomography in the assessment of penile cavernous fibrosis in a rabbit castration model

“…We chose TGF‐beta‐1 expression for CF assessment, as this pleiotropic cytokine has been shown to induce collagen synthesis in cavernosal tissue in vitro 30,31 . Also, TGF‐beta‐1 overexpression is associated with CF occurrence in animal and human studies, making it one of the CF markers 9,32,33 . Unfortunately, it was technically impossible to conduct RT‐PCR to analyze TGF‐beta‐1 expression due to the absence of RNA in penile tissue samples that underwent micro‐CT.…”

“…30,31 Also, TGF-beta-1 overexpression is associated with CF occurrence in animal and human studies, making it one of the CF markers. 9,32,33 Unfortunately, it was technically impossible to conduct RT-PCR to analyze TGF-beta-1 expression due to the absence of RNA in penile tissue samples that underwent micro-CT. RNA disruption during micro-CT was the reason why TGF-beta-1 expression analysis could not be performed and also provoked low efficiency of DNase processing, probably due to the formation of crosslinks in the DNA, making it inaccessible to DNase. 34 The study's main aim was to compare the capabilities of micro-CT imaging and radiodensity assessment for CF evaluation in the whole penile sample with the following analysis by acknowledged methods, such as histological, histochemical, immunohistochemical, and RT-PCR evaluation.…”

“…Also, the time intervals of taking penile samples for these purposes vary depending on the CF model because of different dynamics of fibrogenesis caused by pathology in NO‐cGMP, TGF‐β, SHH, VEGF, and ROCK signaling pathways 6 . For instance, while CF occurs rapidly following cavernous nerve injury and castration within 2–4 weeks, 7,8 in diabetes mellitus, similar morphological changes can be observed within 6–12 weeks, 9,10 and in aging signs of CF could be detected throughout the entire life of laboratory animals 11 …”