title: In vitro effects of a novel class of nitric oxide (NO) donating compounds on isolated human erectile tissue.
abstract: OBJECTIVE
  The discovery of nitric oxide (NO) as one of the major effectors in penile erectile function has led to the development of various drugs which are able to elevate intracellular levels of cGMP. Recently, a novel class of NO donors have been developed, exemplified by S-nitroso-glutathione (GSNO) and S-nitroso-N-acetylcysteine-ethylester (SNACET), as well as compounds combining both phosphodiesterase inhibitory and NO donating activity, such as NCX 911 (sildenafil nitrate). In our study, we assessed the effects of GSNO, SNACET and NCX 911 on adrenergic tension and electrically induced relaxation of isolated human corpus cavernosum (HCC) and the in vitro formation of cGMP. Effects were compared to those of sodium nitroprusside (SNP) and sildenafil citrate.
  
  
  METHODS
  Using the organ bath technique, drug effects were investigated on norepinephrine-induced tension and electrically induced relaxation of HCC. HCC strips were exposed to increasing concentrations of the compounds (0.01/0.1-10/100 microM) and the accumulation of cGMP was determined by means of a radioimmunoassay.
  
  
  RESULTS
  Relaxation of HCC induced by means of electrical field stimulation (EFS) was abolished by tetrotodoxin, guanylyl cyclase inhibitor ODQ and nitric oxide synthase inhibitor L-NNA. Adrenergic tension of HCC strips was dose-dependently reversed by the drugs. The rank order of potency was: SNP > GSNO > NCX911 > sildenafil > SNACET. Compounds also dose-dependently increased EFS-induced amplitudes of relaxation (SNP > NCX911 > sildenafil > SNACET/GSNO). Relaxing effects of the drugs were paralleled by an increase in tissue levels of cGMP.
  
  
  CONCLUSIONS
  Our results provide a rationale for future use of NCX 911 and S-nitrosothiols in the pharmacotherapy of erectile dysfunction (ED). Since the compounds are assumed to exert no considerable hemodynamic effects, they might be developed into new oral treatments for ED.
authors.affiliation: Depatment of Urology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Seidler
authors.forename: Stefan
authors.initials: S
authors.lastname: Uckert
authors.forename: Eginhard
authors.initials: E
authors.lastname: Waldkirch
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelke
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
authors.forename: Michael
authors.initials: M
authors.lastname: Sohn
authors.forename: Udo
authors.initials: U
authors.lastname: Jonas
mesh_terms: D000328:Adult; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism*; D004558:Electric Stimulation; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
chemical_list: D020030:Nitric Oxide Donors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D006152:Cyclic GMP