Korean J Androl.  2005 Apr;23(1):24-29.

Expression of Hypoxia-inducible Factor-1alpha and Vascular Endothelial Growth Factor in Corpus Cavernosum of the Type 2 Diabetes Mellitus Rat

• Lee WK
• Ko KT
• Lee SW
• Seo CD
• Kim SY
• Kim H
• Yang DY
• Kim DM

Abstract

PURPOSE
The expression of hypoxia-inducible factor-1alpha(HIF-1alpha) and vascular endothelial growth factor(VEGF) has been known as important factor of vascular complications in diabetes mellitus. The penile tumescence has variable degree according to vascularity. The aims of this study were to investigate erectile function and cavernosal expression of HIF-1alpha and VEGF in Otsuka Long-Evans Tokushima Fatty(OLETF) rats, which develop NIDDM naturally.
MATERIALS AND METHODS
Ten male OLETF rats and ten control male Long-Evans Tokushima Fatty(LETO) rats were included in this study. The development of diabetes mellitus for OLETF were defined by glucose tolerance test at 26 weeks. After 72 weeks, OLETF rats, LETO rats and ten twenty-week male Sprague-Dawley rats were studied. Intracavernosal pressure were measured after cavernous nerve stimulation. Immunohistochemical stain and Western blot analysis were done for HIF-1alpha and VEGF in corpus cavernosum.
RESULTS
Cavernous nerve stimulation-induced mean intracavernosal pressure(mmHg) was significantly decreased in the OLETF group(21.6+/-6.7 mmHg) compared to LETO(32.8+/-16.0 mmHg) group and in the LETO group compared to Sprague-Dawley group(47.2+/-11.7 mmHg)(p <0.05). With Western blot analysis, HIF-1alpha and VEGF expressions were higher in the OLETF group compared to other groups. With immunohistochemical stain, HIF-1alpha and VEGF were mainly expressed in corpus cavernosum and endothelium.
CONCLUSIONS
We propose that increased HIF-1alpha and VEGF expressions in OLETF rat penile tissue can be found at microvascular injury in corpus cavernosum and are presumed to be associated with vasculogenic erectile dysfunction.

Keyword

Diabetes mellitus; Erectile dysfunction; Hypoxia-inducible factor 1; Vascular endothelial growth factor

MeSH Terms

Animals
Blotting, Western
Diabetes Mellitus
Diabetes Mellitus, Type 2*
Endothelium
Erectile Dysfunction
Glucose Tolerance Test
Humans
Hypoxia-Inducible Factor 1
Male
Penile Erection
Rats*
Rats, Inbred OLETF
Rats, Sprague-Dawley
Vascular Endothelial Growth Factor A*
Hypoxia-Inducible Factor 1
Vascular Endothelial Growth Factor A