Vascular endothelial growth factor restores erectile function through inhibition of apoptosis in diabetic rat penile crura.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is known as a multifunctional protein with roles in angiogenesis stimulation and apoptosis inhibition. We hypothesized that intracavernous administration of VEGF would recover erectile dysfunction due to diabetes by protection from apoptosis in the penile cavernosum.


METHODS
A total of 30, 6-month-old male Sprague-Dawley rats were divided into 2 large groups, namely 20 with diabetes and 10 healthy controls. The diabetic group received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Intracavernous injection of VEGF was administered to randomly selected STZ diabetic rats 6 weeks after STZ injections. Erectile functional studies were performed in 10 STZ and 10 STZ plus VEGF rats at 12 weeks. After completion of the functional study the penile crura were collected for molecular and immunohistochemical studies.


RESULTS
Mean intracavernous pressure in the diabetic group was significantly lower than in controls and low pressure was significantly recovered by VEGF treatment. Gene expression of pro-apoptotic and anti-apoptotic factors were present in the control, diabetic and VEGF treated groups. However, anti-apoptotic protein expression was lacking in the diabetic group and it was recovered by VEGF treatment. The apoptotic index in the diabetic group was significantly higher than in controls and this index was significantly decreased in the VEGF treated group.


CONCLUSIONS
The decrease in and recovery of intracavernous pressure correlated significantly with a variation in anti-apoptotic protein expression in the diabetic and VEGF treated groups. To our knowledge this is the first study to show that intracavernous injection of VEGF restores erectile dysfunction through the inhibition of apoptosis in diabetic rats.
Yamanaka
Masaki
M
Department of Urology, Veterans Affairs Medical Center and University of California-San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA. Urologylab@aol.com
Shirai
Masato
M
Shiina
Hiroaki
H
Tanaka
Yuichiro
Y
Enokida
Hideki
H
Tsujimura
Akira
A
Matsumiya
Kiyomi
K
Okuyama
Akihiko
A
Dahiya
Rajvir
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology*; D010413:Penis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A