Arterial erectile dysfunction: different severities of endothelial apoptosis between diabetic patients "responders" and "non responders" to sildenafil

Eur J Intern Med. 2013 Apr;24(3):234-40. doi: 10.1016/j.ejim.2013.01.001. Epub 2013 Jan 26.

Abstract

Background: The low pharmacological response to phosphodiesterase type 5 inhibitors represents an expression of higher endothelial damage in certain categories of patients with erectile dysfunction and high cardiovascular risk. The present study evaluated this objective in type 2 diabetic patients with erectile dysfunction, classified as "non responders" to Sildenafil.

Methods: Eighteen "responder" and twelve "non responder" type 2 diabetic patients were evaluated, relatively to different levels of endothelial damage, through the diagnostic use of a new immunophenotype of circulating endothelial progenitor cells (CD45neg/CD34pos/CD144pos) and endothelial microparticles (CD45neg/CD144pos/Annexin Vpos), recently developed and published by our group.

Results: "Non responder" patients showed a significant higher severity [8.0±3.0 (International Index of Erectile Function-abbreviated version with 5 questions) vs 14.0±3.0] and duration (10.0±2.0 vs 7.0±2.0 years) of erectile dysfunction, higher level of penile arterial insufficiency (peak systolic velocity=13.0±16.0 vs 28.0±26.0cm/s; acceleration time=153±148 vs 125±128 mm/s) and finally a significant higher level of endothelial apoptosis [0.15±0.13 vs 0.05±.0.03% (serum concentrations of endothelial microparticles)] associated with higher serum concentrations of circulating late immunophenotype of endothelial progenitor cells (0.40±0.35 vs 0.12±.0.10%).

Conclusions: The results of this study corroborate the clinical value of the low clinical response to phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction in the patients with high cardiovascular risk profile, such as diabetics. In addition, the markers used in this study confirm their potential application in clinical practice as useful indicators of endothelial alteration. However, in the future we will have to assess a larger number of patients and for a longer period of observation in order to better understand the causal and temporal relations.

MeSH terms

  • Aged
  • Apoptosis
  • Arteries* / drug effects
  • Arteries* / physiopathology
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Cell-Derived Microparticles / metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / physiopathology
  • Diabetic Angiopathies* / physiopathology
  • Drug Resistance
  • Endothelium, Vascular* / metabolism
  • Endothelium, Vascular* / physiopathology
  • Flow Cytometry / methods
  • Humans
  • Impotence, Vasculogenic* / drug therapy
  • Impotence, Vasculogenic* / etiology
  • Impotence, Vasculogenic* / physiopathology
  • Italy
  • Male
  • Middle Aged
  • Penis / blood supply*
  • Phosphodiesterase 5 Inhibitors / administration & dosage
  • Phosphodiesterase 5 Inhibitors / adverse effects
  • Piperazines* / administration & dosage
  • Piperazines* / adverse effects
  • Purines / administration & dosage
  • Purines / adverse effects
  • Risk Factors
  • Severity of Illness Index
  • Sildenafil Citrate
  • Sulfones* / administration & dosage
  • Sulfones* / adverse effects
  • Treatment Outcome

Substances

  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Sildenafil Citrate