Male Reproductive Tract

Phosphorylated Endothelial Nitric Oxide Synthase Mediates Vascular Endothelial Growth Factor-Induced Penile Erection

Abstract
The objective of this study was to evaluate whether vascular endothelial growth factor (VEGF)-induced penile erection is mediated by activation of endothelial nitric oxide synthase (eNOS) through its phosphorylation. We assessed the role of constitutively activated eNOS in VEGF-induced penile erection using wild type (WT) and eNOS-deficient (eNOS^-/-) mice with and without vasculogenic erectile dysfunction. Adult WT and eNOS^-/- mice were subjected to sham operation or bilateral castration to induce vasculogenic erectile dysfunction. At the time of surgery, animals were injected intracavernosally with a replication-deficient adenovirus expressing human VEGF145 (10⁹ particle units), or with empty virus (Ad.Null). After seven days, erectile function was assessed in response to cavernous nerve electrical stimulation. Total and phosphorylated protein kinase B (Akt) and total and phosphorylated eNOS were quantitatively assessed in mice penes using Western immunoblot and immunohistochemistry. VEGF145 significantly increased erectile responses in intact WT mice and completely recovered penile erection in WT mice after castration. However, VEGF145 failed to increase erectile responses in intact eNOS^-/- mice and only partially recovered erectile function in castrated eNOS^-/- mice. In addition, VEGF significantly increased phosphorylation of eNOS at Serine 1177 about two-fold in penes of both intact and castrated WT mice. The data provide a molecular explanation for VEGF stimulatory effect on penile erection, which involves phosphorylated eNOS (Serine 1177) mediation.

Key words: Male Reproductive Tract • Growth factors • Nitric oxide • Penis • Signal transduction

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