Abstract
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.
source: https://www.ncbi.nlm.nih.gov/pubmed/19912487