Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

The purpose of the current study was to evaluate the effect of a high-fat （HF） diet, energy restriction and exercise on the expression of vascular endothelial growth factor （VEGF）, angiopoietin （Ang） I and 2, and their receptors in rat corpus cavernosum （CC）. Male Wistar rats were fed adlibitum with an H F diet for 8 or 16 weeks. After 8 weeks of the H F diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays （VEGF, VEGF receptor （VEGFR） I and 2, Angl, Ang2 and Tie2） and semiquantification of VEGF, VEGFR 1, VEGFR2, Angl, Ang2, Tie2, endothelial nitric oxide synthase （eNOS） and Aktlphospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol （HDL-c） levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.