title: TNF-alpha infusion impairs corpora cavernosa reactivity.
abstract: BACKGROUND
  Erectile dysfunction (ED), as well as cardiovascular diseases (CVDs), is associated with endothelial dysfunction and increased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha).
  
  
  OBJECTIVE
  We hypothesized that increased TNF-alpha levels impair cavernosal function.
  
  
  METHODS
  In vitro organ bath studies were used to measure cavernosal reactivity in mice infused with vehicle or TNF-alpha (220 ng/kg/min) for 14 days. Gene expression of nitric oxide synthase isoforms was evaluated by real-time polymerase chain reaction.
  
  
  METHODS
  Corpora cavernosa from TNF-alpha-infused mice exhibited decreased nitric oxide (NO)-dependent relaxation, which was associated with decreased endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) cavernosal expression.
  
  
  RESULTS
  Cavernosal strips from the TNF-alpha-infused mice displayed decreased nonadrenergic-noncholinergic (NANC)-induced relaxation (59.4 +/- 6.2 vs. control: 76.2 +/- 4.7; 16 Hz) compared with the control animals. These responses were associated with decreased gene expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated, as well as phenylephrine (PE)-induced, contractile responses (PE-induced contraction; 1.32 +/- 0.06 vs. control: 0.9 +/- 0.09, mN) were increased in cavernosal strips from TNF-alpha-infused mice. Additionally, infusion of TNF-alpha increased cavernosal responses to endothelin-1 and endothelin receptor A subtype (ET(A)) receptor expression (P < 0.05) and slightly decreased tumor necrosis factor-alpha receptor 1 (TNFR1) expression (P = 0.063).
  
  
  CONCLUSIONS
  Corpora cavernosa from TNF-alpha-infused mice display increased contractile responses and decreased NANC nerve-mediated relaxation associated with decreased eNOS and nNOS gene expression. These changes may trigger ED and indicate that TNF-alpha plays a detrimental role in erectile function. Blockade of TNF-alpha actions may represent an alternative therapeutic approach for ED, especially in pathologic conditions associated with increased levels of this cytokine.
authors.affiliation: Institute of Biomedical Sciences, University of Sao Paulo, Pharmacology, Sao Paulo, SP, Brazil. fcarneiro@mcg.edu
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Carneiro
authors.forename: Saiprazad
authors.initials: S
authors.lastname: Zemse
authors.forename: Fernanda R C
authors.initials: FR
authors.lastname: Giachini
authors.forename: Zidonia N
authors.initials: ZN
authors.lastname: Carneiro
authors.forename: Victor V
authors.initials: VV
authors.lastname: Lima
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression; D066298:In Vitro Techniques; D007267:Injections; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010413:Penis / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase