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Asian Journal of Andrology (2012) 14, 635-642; doi:10.1038/aja.2011.131; published online 5 December 2011
Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats
Inês Tomada1,2, Nuno Tomada1,2,3, Henrique Almeida1,2 and Delminda Neves1,2
1 Department of Experimental Biology, Faculty of Medicine, Universidade do Porto—Alameda Prof, Hernâni Monteiro, Porto 4200-319, Portugal
2 Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto—Rua do Campo Alegre 823, Porto 4150-180, Portugal
3 Department of Urology, Centro Hospital S. João, EPE - Alameda Professor, Hernâni Monteiro, Porto 4200-319, Portugal
Correspondence: Dr I Tomada, (inestomada@gmail.com)
Received 23 May 2011; Revised 11 July 2011; Accepted 12 August 2011
Advance online publication 5 December 2011.
| Abstract |
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) 1 and 2, and their receptors in rat corpus cavernosum (CC). Male Wistar rats were fed ad libitum with an HF diet for 8 or 16 weeks. After 8 weeks of the HF 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) 1 and 2, Ang1, Ang2 and Tie2) and semiquantification of VEGF, VEGFR1, VEGFR2, Ang1, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and Akt/phospho-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.
Keywords: angiopoietins; corpus cavernosum; endothelial dysfunction; energy restriction; exercise; high-fat diet; VEGF |
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