Endothelial Nitric Oxide Synthase Keeps Erection Regulatory Function Balance in the Penis

ObjectivesWe 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.MethodsFour groups of mice were used: wild type (WT), 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-α and -β 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.ResultsCompared 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-α and -β protein expressions. After eNOS gene transfer to penes of eNOS−/− mice, Rho-kinase-β and p-MYPT-1 expressions and total Rho-kinase activity were significantly increased from baseline levels (p < 0.05).ConclusionsThese data suggest that endothelial NO has a role in the penis as a regulator of the basal signaling functions of the NO and RhoA/Rho-kinase erection mediatory pathways. These data offer new insight into the homeostasis of erection regulatory biology.