Endothelial nitric oxide synthase keeps erection regulatory function balance in the penis

Objectives: We evaluated the regulatory influence of endothelial nitric oxide (NO) on the basal functional states of the NO and RhoA/Rho-kinase signaling pathways in the penis using endothelial No synthase (eNOS) mutant mice and eNOS gene transfer technology. Methods: Four groups of mice were used: wild type (VIT), eNOS gene deleted (eNOS(-/-)), eNOS and neuronal NOS gene deleted (dNOS(-/-)), and eNOS(-/-) mutant mice transfected intracavernosally with eNOS. Cyclic guanosine monophosphate (cGMP) concentration, protein kinase G (PKG) activity, activated RhoA, and Rho-kinase activity were determined in penes of WT and both mutant mouse groups. Constitutive NOS and PKG activities, RhoA, Rho-kinase-alpha and -beta isoforms, and phosphorylated myosin light-chain phosphatase target subunit (p-MYPT-1) expressions and Rho-kinase activity were determined in penes of eNOS-/- mice after eNOS gene transfer. Results: Compared with results in the WT penis, eNOS(-/-) and dNOS(-/-) mutant mouse penes had significant reductions in NOS activity, cGMP concentration, PKG activity, Rho-kinase activity, and p-MYPT-1 expression (p < 0.05) with no significant changes in activated RhoA or in RhoA and Rho-kinase-alpha and -beta protein expressions. After eNOS gene transfer to penes of eNOS-/- mice, Rho-kinase-beta and p-MYPT-1 expressions and total Rho-kinase activity were significantly increased from baseline levels (p < 0.05). Conclusions: These data suggest that endothelial NO has a role in the penis as a regulator of the basal signaling functions of the No and RhoA/Rhokinase erection mediatory pathways. These data offer new insight into the homeostasis of erection regulatory biology.