PMID- 19170842
OWN - NLM
STAT- MEDLINE
DCOM- 20090713
LR  - 20211020
IS  - 1743-6109 (Electronic)
IS  - 1743-6095 (Print)
IS  - 1743-6095 (Linking)
VI  - 6
IP  - 1
DP  - 2009 Jan
TI  - TNF-alpha knockout mice have increased corpora cavernosa relaxation.
PG  - 115-25
LID - 10.1111/j.1743-6109.2008.01029.x [doi]
AB  - INTRODUCTION: Erectile dysfunction is considered an early clinical manifestation 
      of vascular disease and an independent risk factor for cardiovascular events 
      associated with endothelial dysfunction and increased levels of pro-inflammatory 
      cytokines. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, 
      suppresses endothelial nitric oxide synthase (eNOS) expression. AIM: Considering 
      that nitric oxide (NO) is of critical importance in penile erection, we 
      hypothesized that blockade of TNF-alpha actions would increase cavernosal smooth 
      muscle relaxation. METHODS: In vitro organ bath studies were used to measure 
      cavernosal reactivity in wild type and TNF-alpha knockout (TNF-alpha KO) mice and 
      NOS expression was evaluated by western blot. In addition, spontaneous erections 
      (in vivo) were evaluated by videomonitoring the animals (30 minutes). Collagen 
      and elastin expression were evaluated by Masson trichrome and Verhoff-van Gieson 
      stain reaction, respectively. MAIN OUTCOME MEASURES: Corpora cavernosa from 
      TNF-alpha KO mice exhibited increased NO-dependent relaxation, which was 
      associated with increased eNOS and neuronal NOS (nNOS) cavernosal expression. 
      RESULTS: Cavernosal strips from TNF-alpha KO mice displayed increased 
      endothelium-dependent (97.4 +/- 5.3 vs. CONTROL: 76.3 +/- 6.3, %) and 
      nonadrenergic-noncholinergic (93.3 +/- 3.0 vs. CONTROL: 67.5 +/- 16.0; 16 Hz) 
      relaxation compared to control animals. These responses were associated with 
      increased protein expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated 
      (0.69 +/- 0.16 vs. CONTROL: 1.22 +/- 0.22; 16 Hz) as well as 
      phenylephrine-induced contractile responses (1.6 +/- 0.1 vs. CONTROL: 2.5 +/- 
      0.1, mN) were attenuated in cavernosal strips from TNF-alpha KO mice. 
      Additionally, corpora cavernosa from TNF-alpha KO mice displayed increased 
      collagen and elastin expression. In vivo experiments demonstrated that TNF-alpha 
      KO mice display increased number of spontaneous erections. CONCLUSION: Corpora 
      cavernosa from TNF-alpha KO mice display alterations that favor penile 
      tumescence, indicating that TNF-alpha plays a detrimental role in erectile 
      function. A key role for TNF-alpha in mediating endothelial dysfunction in ED is 
      markedly relevant since we now have access to anti-TNF-alpha therapies.
FAU - Carneiro, Fernando S
AU  - Carneiro FS
AD  - Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo; Sao 
      Paulo, SP, Brazil. fcarneiro@mcg.edu
FAU - Sturgis, Lashon C
AU  - Sturgis LC
FAU - Giachini, Fernanda R C
AU  - Giachini FR
FAU - Carneiro, Zidonia N
AU  - Carneiro ZN
FAU - Lima, Victor V
AU  - Lima VV
FAU - Wynne, Brandi M
AU  - Wynne BM
FAU - San Martin, Sebastian
AU  - San Martin S
FAU - Brands, Michael W
AU  - Brands MW
FAU - Tostes, Rita C
AU  - Tostes RC
FAU - Webb, R Clinton
AU  - Webb RC
LA  - eng
GR  - R01 HL071138/HL/NHLBI NIH HHS/United States
GR  - R01 HL071138-06/HL/NHLBI NIH HHS/United States
GR  - HL71138/HL/NHLBI NIH HHS/United States
GR  - HL74167/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Sex Med
JT  - The journal of sexual medicine
JID - 101230693
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-34-5 (Collagen)
RN  - 9007-58-3 (Elastin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Collagen/metabolism
MH  - Elastin/metabolism
MH  - Endothelium, Vascular/immunology/metabolism/pathology
MH  - Erectile Dysfunction/*immunology/metabolism/*therapy
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth/*immunology/metabolism/pathology
MH  - Nitric Oxide Synthase/metabolism
MH  - Penis
MH  - Tumor Necrosis Factor-alpha/*immunology
MH  - Vasodilation/*physiology
PMC - PMC2843140
MID - NIHMS170297
EDAT- 2009/01/28 09:00
MHDA- 2009/07/14 09:00
PMCR- 2010/03/22
CRDT- 2009/01/28 09:00
PHST- 2009/01/28 09:00 [entrez]
PHST- 2009/01/28 09:00 [pubmed]
PHST- 2009/07/14 09:00 [medline]
PHST- 2010/03/22 00:00 [pmc-release]
AID - S1743-6095(15)32253-0 [pii]
AID - 10.1111/j.1743-6109.2008.01029.x [doi]
PST - ppublish
SO  - J Sex Med. 2009 Jan;6(1):115-25. doi: 10.1111/j.1743-6109.2008.01029.x.