title: Endothelial nitric oxide synthase keeps erection regulatory function balance in the penis.
abstract: OBJECTIVE
  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 (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-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/Rho-kinase erection mediatory pathways. These data offer new insight into the homeostasis of erection regulatory biology.
authors.affiliation: The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Hospital, Baltimore, MD 21287, United States.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.forename: Tongyun
authors.initials: T
authors.lastname: Liu
authors.forename: Biljana
authors.initials: B
authors.lastname: Musicki
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Champion
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Burnett
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000201:enzymology* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; D020742:rhoA GTP-Binding Protein; D006152:Cyclic GMP