title: Sildenafil, a type-5 CGMP phosphodiesterase inhibitor, specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro.
abstract: OBJECTIVE
  The primary mechanism for relaxation of corpus cavernosum smooth muscle (CCSM) and penile erection depends upon nitric oxide (NO)-induced elevation of myoplasmic cyclic guanosine monophosphate (cGMP). Agents that enhance the NO-cGMP signal transduction pathway may prove beneficial in treating erectile dysfunction. Sildenafil, a selective type-5 cGMP phosphodiesterase inhibitor, was investigated to determine the specific mechanism(s) involved in the therapeutic use of this compound to treat impotence.
  
  
  METHODS
  Isolated strips of rabbit corpus cavernosum were stimulated isometrically with phenylephrine. Graded relaxations were induced using various concentrations of sodium nitroprusside (SNP) alone and in combination with sildenafil. At fixed times, the tissues were rapidly frozen and processed for myosin light chain (MLC) phosphorylation using isoelectric focusing with Western blot analysis, and cGMP content using radioimmunoassay techniques.
  
  
  RESULTS
  Sildenafil alone reduced spontaneous tone in unstimulated CCSM, but had little effect on phenylephrine-induced isometric tension in the absence of a NO donor (SNP). Sildenafil sensitized the tissue to SNP for relaxation, but the relationship between relaxation and [cGMP] was unchanged by sildenafil. Relaxation from peak isometric force was correlated with [cGMP] but not MLC phosphorylation.
  
  
  CONCLUSIONS
  Sildenafil relaxes CCSM by amplifying the effects of the normal, endogenous cGMP dependent relaxation mechanisms.
authors.affiliation: Department of Urology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Chuang
authors.forename: J D
authors.initials: JD
authors.lastname: Strauss
authors.forename: R A
authors.initials: RA
authors.lastname: Murphy
authors.forename: W D
authors.initials: WD
authors.lastname: Steers
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010413:Penis / Q000187:drug effects* / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones
chemical_list: D004791:Enzyme Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D006152:Cyclic GMP