Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries

J Sex Med. 2010 Feb;7(2 Pt 1):758-68. doi: 10.1111/j.1743-6109.2009.01587.x. Epub 2009 Nov 12.


Introduction: Diabetic men with erectile dysfunction (ED) are less responsive to therapy with type 5 phosphodiesterase (PDE5) inhibitors. Although an impairment of the nitric oxide (NO)/cyclic guanosin-monophosphate (cGMP) pathway has been shown in diabetic ED vs. non-diabetic ED, the functionality of NO/cGMP pathway in non-diabetic and diabetic ED patients with respect to non-ED patients has not been established.

Aim: The aim of this study is to evaluate the function of NO/cGMP signalling in human erectile tissues from ED patients exploring the added impact of diabetes.

Methods: Corpus cavernosum strips (human corpus cavernosum [HCC]) and penile resistance arteries (HPRA) were collected from penile specimens from organ donors (OD) and from diabetic and non-diabetic men with ED undergoing penile prosthesis implantation.

Main outcome measures: Relaxations to acetylcholine, electrical field stimulation, sodium nitroprusside, and sildenafil were evaluated in phenylephrine-contracted HCC and norepinephrine-contracted HPRA. cGMP content in HCC was also determined.

Results: The impairment of endothelium-dependent relaxation in HCC and HPRA from ED patients was exacerbated by diabetes (E(max) 76.1, 62.9, and 49.3% in HCC and 73.1, 59.8, and 46.0% in HPRA from OD, non-diabetic and diabetic ED, respectively). Hypertension, hypercholesterolemia, or aging did not exert a further impairment of endothelial relaxation among ED patients. Diabetes also causes a further impairment of neurogenic relaxation in HCC and HPRA. The basal and stimulated content of cGMP in HCC was significantly decreased in patients with ED, but specially reduced in diabetic patients. Diabetes clearly impaired PDE5 inhibitor-induced vasodilation of HPRA from ED patients.

Conclusions: ED is related to impaired vasodilation, reduced relaxant capacity, and diminished cGMP content in penile tissue. These alterations are more severe in diabetes and accompany reduced relaxant efficacy of PDE5 inhibition. Thus, an exacerbated reduction of nitric oxide/cGMP signaling could be responsible for ED in diabetic men and would explain their reduced response to treatment.

MeSH terms

  • Adult
  • Cyclic GMP / physiology*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Angiopathies / physiopathology*
  • Diabetic Neuropathies / physiopathology
  • Humans
  • Impotence, Vasculogenic / physiopathology*
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiopathology
  • Nitric Oxide / physiology*
  • Penile Implantation
  • Penis / blood supply*
  • Phosphodiesterase 5 Inhibitors
  • Phosphodiesterase Inhibitors / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • Phosphodiesterase 5 Inhibitors
  • Phosphodiesterase Inhibitors
  • Nitric Oxide
  • Cyclic GMP