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

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. 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 microg.) or AAV-BDNF (10 viral particles). Four months later erectile function was evaluated and cavernous tissues were collected for erectile dysfunction and immunohistochemical staining. 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. A high fat diet caused erectile dysfunction with accompanying neurological and vascular changes. VEGF and AAV-BDNF seemed to alleviate these problems.