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

Trinity J. Bivalacqua, Tongyun Liu, Biljana Musicki, Hunter C. Champion, Arthur L. Burnett

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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 (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. 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-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). 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.

Original languageEnglish (US)
Pages (from-to)1732-1740
Number of pages9
JournalEuropean Urology
Issue number6
StatePublished - Jun 2007


  • Erectile dysfunction
  • Nitric oxide
  • PKG
  • Priapism
  • Rho-kinase
  • RhoA
  • eNOS

ASJC Scopus subject areas

  • Urology


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