Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk

Abstract

The number of the circulating angiogenic cells (CACs) and colony forming units (CFUs) derived from cultured circulating mononuclear cells (MNCs) represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction (ED) and vascular risk factors (VRFs) showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4 weeks of treatment with tadalafil (20 mg every other day) or with a placebo. The tadalafil treatment improved erectile function (P = 0.0028), but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 (P = 0.011) and tissue type plasminogen activator (P = 0.005) were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.

Endothelial Dysfunction in Patients With Erectile Dysfunction: A Double-Blind, Randomized-Control Trial Using Tadalafil

“…Nevertheless, the baseline FMD was similar in both the groups and we did not find tadalafil to improve the brachial FMD significantly compared with placebo. Although our study falls in line with the other studies by Pecilline et al 16 that evaluated the markers of endothelial repair and the integrated analysis by Prost et al 18 suggesting no effect of tadalafil on EnD, both the studies did not use FMD for assessments.…”

“…EnD, the final common pathway for manifestation of ED, has been a fertile area of research in the recent years. However, the evidence so far has been conflicting 10, 11, 13, 14, 15, 16. Studies have also suggested that low-dose daily tadalafil is safe and efficacious, thereby providing a steady-state level of drug for its beneficial effect on ED; also, such a measure could actually improve EnD 12 .…”

“…Based on evidence, it has been hypothesized that chronic use of PDEI may be beneficial for ED subjects 10 . 2 studies have demonstrated that EnD as measured by brachial artery FMD improved significantly with daily use of tadalafil over 4–6 weeks14, 15 and conversely there are studies with contrasting findings suggesting that the effect of tadalafil on markers of EnD is modest 16, 17, 18. Considering the limitations of the earlier reported studies, this study was conducted to evaluate the effect of tadalafil on brachial artery FMD.…”

The efficacy of low-dose tadalafil in patients undergoing hemodialysis with end-stage renal disease

“…In contrast with this report, Pelliccione et al. claimed that tadalafil had only a modest effect on endothelial recovery [37]. Our results suggested that optimum effort must be made to guard against other cardiovascular risk factors, such as hypertension and hyperlipidemia, which promote endothelial dysfunction, in addition to using tadalafil treatment in patients with ESRD.…”

Insights on Protective Effect of Platelet Rich Plasma and Tadalafil on Testicular Ischemia/Reperfusion Injury in Rats Exposed to Testicular Torsion/Detorsion

“…Earlier studies demonstrate PDE5 inhibition down-regulates the endothelium system [60,61], which clarifies E-selectin reduced levels in the rats with I-R injury treated with PDE5i. Whereas available studies, including our research, documented the reduction of biochemical measures of endothelial activation/damage system in the testes injury treated with PDE5i, which are sPlatelet (P)-selectin, sE-selectin and s-Intercellular adhesion molecule-1 (ICAM-1) [62][63][64]. This finding is confirmed in our data and established that the E-selectin levels were returned below those observed in the TDP group, even though its quantifiable significance has yet to be distinct compared to the healthy groups.…”