Effects of Tadalafil on Platelets and Endothelium in Patients With Erectile Dysfunction and Cardiovascular Risk Factors: A Pilot Study

Abstract

Activation of endothelial cells and platelets is an initial step toward the development of cardiovascular disease. Erectile dysfunction (ED) may be an early manifestation of endotheliopathy. We evaluated the effects of tadalafil on cyclic nucleotides (cGMP and cAMP) and soluble adhesion molecules (E- and P-selectin [ES and PS]). The patients were divided into 2 groups on the basis of the presence (10 patients) or absence (9 patients) of cardiovascular risk factors (dyslipidemia, hypertension, and smoking). Nitric oxide (NO) was unmeasurable in all the patients. Tadalafil administration induced a significant increase in cGMP levels in both groups (P < .01). In contrast, cAMP significantly increased (P < .05) and PS decreased (P < .01) only in patients without cardiovascular risk factors. Tadalafil induced a beneficial effect on platelet activation in patients with ED without cardiovascular risk factors; this effect was not mediated by NO.

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

“…Whereas available studies, including this one, documented a reduced level of ET-1 in ED patients treated with PDE5i,151734 conflicting results were obtained when biochemical measures of endothelial activation/damage other than ET-1 were considered. The levels of sE-selectin,1718 sPlatelet (P)-selectin and s-Intercellular adhesion molecule-1 (ICAM-1) were not altered in the ED men with VRFs treated with PDE5i;1836 whereas, the same treatment was associated with reduced levels of sICAM,19 sP-selectin and sVascular cell adhesion molecule-1 (VCAM-1) 1837. A limitation in these trials is the lack of a healthy group to determine whether the levels of CAMs released by the endothelial cells were elevated in ED men.…”

“…This finding suggests reconsidering the hypothesis that PDEi has a beneficial effect on vascular homeostasis relying on surrogate measures such as biochemical and/or functional parameters of endothelium health 111516171819. Whether PDE5i treatment has a clinically relevant positive effect on vascular health should be investigated by longitudinal studies that have the clinical measures of vascular health as primary outcomes.…”

“…Selective inhibitors (i) of phosphodiesterase type 5 (PDE5) in men with ED and VRFs are effective in treating ED, while improving the endothelial function at the brachial arteries and reducing the biochemical measures of endothelial cell damage/dysfunction 111516171819. These agents competitively inhibit cyclic guanosine 5’- monophosphate hydrolysis by PDE5, thereby fostering NO-dependent cyclic guanosine 5’- monophosphate accumulation and the consequent relaxation of vascular smooth muscle cells 20.…”

“…As a secondary outcome, we explored the effect of tadalafil treatment on the circulating markers of endothelial cell damage/dysfunction. The aim of the study was to explore the potential effects of PDE5 inhibition on the laboratory surrogates of endothelial cell damage and repair ability to lend support to the hypothesis of a beneficial effect of this inhibition on vascular homeostasis 111516171819…”

Efficacy of Pentoxifylline and Tadalafil in Rat Model of Ischemic ColITIS

“…The efficacy of the drugs is considered to be the likely result of the common effects of these two drugs; namely, the inhibition of platelet aggregation, as well as the other well-known major effects associated with them. De Bon E et al showed the effect of tadalafil on platelets and its useful effects on vascular endothelial ischemic damage [20]. In the study performed by JG Adams Jr et al to investigate Tadalafil and Ischemic Colitis 353 the effect of pentoxifylline in the ischemic reperfusion model, the efficacy of pentoxifylline was proved by the inhibition of platelet-activating factor (PAF) [21].…”