Vascular endothelial growth factor restores corporeal smooth muscle function in vitro

Purpose: The therapeutic use of vasculogenic growth factors has been succes sfully demonstrated in models of organ ischemia. We determined whether vasc ular endothelial growth factor (VEGF) would reverse corporeal smooth muscle dysfunction in the hypercholesterolemic rabbit model of erectile dysfuncti on. Materials and Methods: A total of 36 New Zealand White rabbits were fed a n ormal (12) or 1% cholesterol (24) diet and treated after 6 weeks with 0.9 m g. VEGF or vehicle. At 6 weeks 24 rabbits received a single intracavernous dose and 12 received a single intravenous bolus of either drug. Ten days af ter injection corporeal smooth muscle function was analyzed after relaxatio n to acetylcholine and sodium nitroprusside using isometric tension studies . Corporeal sections were assessed for smooth muscle content with f-actin s taining and VEGF expression by immunohistochemical study and enzyme-linked immunosorbent assay. Results: Endothelium dependent (acetylcholine) and nitric oxide mediated (s odium nitroprusside) smooth muscle relaxation were impaired in cholesterol fed animals (p = 0.021 and 0.003, respectively). Intracavernous VEGF treatm ent restored sodium nitroprusside mediated relaxation to normal(p = 0.015) and intravenous VEGF restored acetylcholine and sodium nitroprusside mediat ed relaxation (p = 0.014 and 0.018, respectively). Decreased smooth muscle content was noted in cholesterol fed animals versus normal diet controls (p = 0.008), which was not affected by VEGF treatment (p = 0.450). Corporeal endothelial cell content was increased after intracavernous but not intrave nous VEGF treatment (p = 0.001 and 0.385, respectively). VEGF expression wa s augmented after treatment with recombinant VEGF (p <0.001). Conclusions: VEGF administration variably mitigated the impairment of corpo real smooth muscle relaxation in the hypercholesterolemic rabbit model of e rectile dysfunction.