Decreases in corporeal vascular endothelial growth factor expression precede vasoreactivity changes in cholesterol fed rabbits

Purpose: We determined temporal changes in vasoreactivity and angiogenic growth factor levels in corporeal tissue at varying time points after the induction of hypercholesterolemia in rabbits. Materials and Methods: A total of 42 New Zealand White rabbits were fed a 1% cholesterol (8 per group) or normal (6 per group) diet for 2, 4.5 or 7.5 weeks. Vascular endothelial growth factor (VEGF) mRNA expression in corpus cavernosum was assessed by real-time polymerase chain reaction analyses for the 3 isoforms VEGF₁₂₁, VEGF ₁₆₅ and VEGF₁₈₉. Isometric tension studies were performed and dose response curves were generated to evaluate endothelial dependent and endothelial independent vasoreactivity. Results: Real-time polymerase chain reaction analysis showed 2.2 to 2.5 and 1.5 to 2.7-fold decreases in VEGF ₁₂₁ and VEGF₁₆₅, respectively, in the corporeal tissues of the high cholesterol group vs the normal diet group at the 2 week time point. At 2 weeks VEGF₁₈₉ was unchanged but it was decreased 1.5 to 2-fold at 4.5 weeks. Acetylcholine isometric tension studies revealed no difference in mean ED₅₀ (-log [M]) ± SD until 7.5 weeks of high cholesterol diet (5.10 ± 0.64 vs 3.95 ± 1.35, p = 0.0269). The response to sodium nitroprusside was not statistically different at any time point. Endothelial cell and smooth muscle content were decreased for the high cholesterol vs normal diet at 4.5 weeks (endothelial only) and 7.5 weeks (each cell). Conclusions: Alterations in corporeal tissue levels of VEGF occur before abnormalities in vasoreactivity. The results suggest that VEGF has a role in normal vasoreactivity in corporeal tissue and, thereby, in normal erectile function.