Endothelial rehabilitation: the impact of chronic PDE5 inhibitors on erectile function and protein alterations in cavernous tissue of diabetic rats.
BACKGROUND
Diabetic men generally have reduced efficacy with PDE-5 inhibitors (PDE5i) for the treatment of erectile dysfunction (ED).


OBJECTIVE
To determine whether chronic vardenafil exposure alters cavernous protein expression predicting improved erectile function in diabetes.


METHODS
Forty-two adult male Sprague Dawley rats with streptozotocin-induced (50mg/kg IP) diabetes for 4 wk, were exposed to either vehicle or vardenafil for 6 wk. Assessments compared the impact of vardenafil given at 1h and 20 h to erectile function and cellular alterations and downstream translation of cavernous protein profiles were aimed.


METHODS
Vehicle or vardenafil 0.5mg/kg/day by oral gavage for 6 wk.


METHODS
Erectile function, penile tissue morphology, protein expression and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) protein profiling were determined.


CONCLUSIONS
A significant increase of intracavernous pressure was seen in both treatment arms compared to diabetic rats not receiving vardenafil. Immunohistochemical staining showed improved endothelial and smooth muscle cell staining with chronic vardenafil use. Western blot analysis demonstrated increased endothelial cell eNOS and smooth muscle alpha-actin protein content. SELDI protein profiling showed enhanced proteins expression at molecular weights of 14.7, 20, 41.9, 66.2, and 83.9 kDa in the chronically treated vardenafil group.


CONCLUSIONS
Vardenafil was effective in treating diabetic-induced ED with the greatest effect achieved through chronic dosing, with no additive effect measured with the final acute dose. Changes noted in the histology and protein expression indicate that vardenafil may have a protective effect in this disease state. This finding may serve as a basis for further work evaluating the utility of chronic vardenafil dosing in diabetic men.
De Young
Ling X
LX
Lawson Health Research Institute, London, ON, Canada; St. Joseph's Health Care, Department of Surgery, Division of Urology, London, ON, Canada.
Domes
Trustin
T
Lim
Kokbin
K
Carson
Jeffery
J
Brock
Gerald B
GB
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013450:Sulfones / Q000008:administration & dosage; D014227:Triazines / Q000008:administration & dosage; D000069058:Vardenafil Dihydrochloride
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride