Age‐Related Changes in Phosphorylation of Endothelial Nitric Oxide Synthase in the Rat Penis

Age‐related ED is associated with eNOS inactivation through a decrease in phosphorylation of its positive regulatory site (Ser‐1177) and an increase in phosphorylation of its negative regulatory site (Thr‐495) in the penis. Altered phosphorylation/constitutive activation of eNOS by fluid shear stress may be a major determinant of compromised vascular homeostasis of the aged penis. The finding that VEGF rapidly induces erection and partly corrects alterations in eNOS phosphorylation in the aged rat penis suggests impaired eNOS activation by deficient endogenous VEGF and supports the potential for growth factor therapy in the treatment of age‐related ED.