The Effect of Vascular Endothelial Growth Factor and Adeno-Associated Virus Mediated Brain Derived Neurotrophic Factor on Neurogenic and Vasculogenic Erectile Dysfunction Induced by Hyperlipidemia
Abstract
Purpose:
We examined neurogenic and vasculogenic erectile dysfunction associated with hypercholesterolemia and evaluated vascular endothelial growth factor (VEGF) and adeno-associated virus (AAV) mediated, brain derived neurotrophic factor (BDNF) for potential treatment.
Materials and Methods:
A total of 21, 2-month-old male rats were fed a 2% cholesterol diet and another seven were fed a normal diet. Two months later serum cholesterol levels were measured and test agents were given intracavernously. Those on normal diet (controls) received phosphate buffered saline (PBS). Those on cholesterol diet were randomly divided into 3 groups receiving PBS, VEGF (4 μg.) or AAV-BDNF (1010 viral particles). Four months later erectile function was evaluated and cavernous tissues were collected for erectile dysfunction and immunohistochemical staining.
Results:
Serum cholesterol levels were higher in rats fed the high fat diet than in controls. Intracavernous pressure was lower in cholesterol plus PBS treated rats than in rats of the other 3 groups. All hypercholesterolemic rats had less nerve content, fewer endothelial cells and higher smooth muscle content than rats with normal cholesterol levels. In cholesterol plus PBS treated rats electron microscopy showed hypermyelination and severe atrophy of axons, a remarkable decrease in the number and size of nonmyelinated axons, disarray of the smooth muscle cells with scant myofilaments and foamy cytoplasm, and denuded endothelial lining of the sinusoids covered by numerous platelets. VEGF and AAV-BDNF appeared to alleviate partially these changes.
Conclusions:
A high fat diet caused erectile dysfunction with accompanying neurological and vascular changes. VEGF and AAV-BDNF seemed to alleviate these problems.
References
- 1 : Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol1994; 140: 930. Google Scholar
- 2 : Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol1991; 146: 238. Link, Google Scholar
- 3 : Relationship between cavernosal ischemia and corporal veno-occlusive dysfunction in an animal model. J Urol1997; 157: 1011. Link, Google Scholar
- 4 : Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction. J Urol1998; 159: 2229. Link, Google Scholar
- 5 : Effect of a Chinese herbal medicine mixture on a rat model of hypercholesterolemic erectile dysfunction. J Urol2000; 164: 1798. Abstract, Google Scholar
- 6 : The effect of adeno-associated virus mediated brain derived neurotrophic factor in an animal model of neurogenic impotence. J Urol2001; 165: 2103. Link, Google Scholar
- 7 : The effect of vascular endothelial growth factor on a rat model of traumatic arteriogenic erectile dysfunction. J Urol2002; 167: 761. Link, Google Scholar
- 8 Rogers, R.S., Graziottin, T.M., Lin, C.-S. et-al: Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Unpublished data Google Scholar
- 9 : Antibodies defining rat endothelial cells: RECA-1, a pan-endothelial cell-specific monoclonal antibody. Lab Invest1992; 66: 459. Google Scholar
- 10 : Primer of Biostatistics. New York: McGraw-Hill1992. Google Scholar
- 11 : The treatment of hypertension in patients with erectile dysfunction. Curr Med Res Opin2000; 16: s31. Google Scholar
- 12 : Endothelial alterations in hypercholesterolemia: more than simply vasodilator dysfunction. J Cardiovasc Pharmacol1998; 32: S48. Google Scholar
- 13 : Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth muscle cell dysfunction. J Urol1994; 151: 198. Link, Google Scholar
- 14 : The vascular biology of nitric oxide and its role in atherogenesis. Annu Rev Med1996; 47: 365. Google Scholar
- 15 : Platelets, oxidant stress and erectile dysfunction: an hypothesis. Cardiovasc Res2000; 46: 50. Google Scholar
From the Department of Urology, University of California, San Francisco, California
