TNF-α infusion impairs corpora cavernosa reactivity

Fernando S. Carneiro, Saiprazad Zemse, Fernanda R.C. Giachini, Zidonia N. Carneiro, Victor V. Lima, R Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Introduction. 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-α). Aim. We hypothesized that increased TNF-α levels impair cavernosal function. Methods. In vitro organ bath studies were used to measure cavernosal reactivity in mice infused with vehicle or TNF-α (220 ng/kg/min) for 14 days. Gene expression of nitric oxide synthase isoforms was evaluated by real-time polymerase chain reaction. Main Outcome Measures. Corpora cavernosa from TNF-α-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-α-infused mice displayed decreased nonadrenergic-noncholinergic (NANC)-induced relaxation (59.4 ± 6.2 vs. control: 76.2 ± 4.7; 16Hz) 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-α-infused mice. Additionally, infusion of TNF-α increased cavernosal responses to endothelin-1 and endothelin receptor A subtype (ETA) receptor expression (P < 0.05) and slightly decreased tumor necrosis factor-alpha receptor 1 (TNFR1) expression (P = 0.063). Conclusion. Corpora cavernosa from TNF-α-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-α plays a detrimental role in erectile function. Blockade of TNF-α actions may represent an alternative therapeutic approach for ED, especially in pathologic conditions associated with increased levels of this cytokine.

Original languageEnglish (US)
Pages (from-to)311-319
Number of pages9
JournalJournal of Sexual Medicine
Volume6
Issue numberSUPPL. 3
DOIs
StatePublished - Jan 1 2009

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Tumor Necrosis Factor-alpha
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Erectile Dysfunction
Phenylephrine
Gene Expression
Cytokines
Endothelin A Receptors
Endothelin Receptors
Tumor Necrosis Factor Receptors
Baths
Nitric Oxide Synthase
Real-Time Polymerase Chain Reaction
Nitric Oxide
Protein Isoforms
Cardiovascular Diseases
Outcome Assessment (Health Care)

Keywords

  • Corpus cavernosum
  • Endothelial nitric oxide synthase
  • Mouse
  • Neuronal nitric oxide synthase
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

Carneiro, F. S., Zemse, S., Giachini, F. R. C., Carneiro, Z. N., Lima, V. V., Webb, R. C., & Tostes, R. C. (2009). TNF-α infusion impairs corpora cavernosa reactivity. Journal of Sexual Medicine, 6(SUPPL. 3), 311-319. https://doi.org/10.1111/j.1743-6109.2008.01189.x

TNF-α infusion impairs corpora cavernosa reactivity. / Carneiro, Fernando S.; Zemse, Saiprazad; Giachini, Fernanda R.C.; Carneiro, Zidonia N.; Lima, Victor V.; Webb, R Clinton; Tostes, Rita C.

In: Journal of Sexual Medicine, Vol. 6, No. SUPPL. 3, 01.01.2009, p. 311-319.

Research output: Contribution to journalArticle

Carneiro, FS, Zemse, S, Giachini, FRC, Carneiro, ZN, Lima, VV, Webb, RC & Tostes, RC 2009, 'TNF-α infusion impairs corpora cavernosa reactivity', Journal of Sexual Medicine, vol. 6, no. SUPPL. 3, pp. 311-319. https://doi.org/10.1111/j.1743-6109.2008.01189.x
Carneiro FS, Zemse S, Giachini FRC, Carneiro ZN, Lima VV, Webb RC et al. TNF-α infusion impairs corpora cavernosa reactivity. Journal of Sexual Medicine. 2009 Jan 1;6(SUPPL. 3):311-319. https://doi.org/10.1111/j.1743-6109.2008.01189.x
Carneiro, Fernando S. ; Zemse, Saiprazad ; Giachini, Fernanda R.C. ; Carneiro, Zidonia N. ; Lima, Victor V. ; Webb, R Clinton ; Tostes, Rita C. / TNF-α infusion impairs corpora cavernosa reactivity. In: Journal of Sexual Medicine. 2009 ; Vol. 6, No. SUPPL. 3. pp. 311-319.
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AU - Carneiro, Fernando S.

AU - Zemse, Saiprazad

AU - Giachini, Fernanda R.C.

AU - Carneiro, Zidonia N.

AU - Lima, Victor V.

AU - Webb, R Clinton

AU - Tostes, Rita C.

PY - 2009/1/1

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N2 - Introduction. 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-α). Aim. We hypothesized that increased TNF-α levels impair cavernosal function. Methods. In vitro organ bath studies were used to measure cavernosal reactivity in mice infused with vehicle or TNF-α (220 ng/kg/min) for 14 days. Gene expression of nitric oxide synthase isoforms was evaluated by real-time polymerase chain reaction. Main Outcome Measures. Corpora cavernosa from TNF-α-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-α-infused mice displayed decreased nonadrenergic-noncholinergic (NANC)-induced relaxation (59.4 ± 6.2 vs. control: 76.2 ± 4.7; 16Hz) 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-α-infused mice. Additionally, infusion of TNF-α increased cavernosal responses to endothelin-1 and endothelin receptor A subtype (ETA) receptor expression (P < 0.05) and slightly decreased tumor necrosis factor-alpha receptor 1 (TNFR1) expression (P = 0.063). Conclusion. Corpora cavernosa from TNF-α-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-α plays a detrimental role in erectile function. Blockade of TNF-α actions may represent an alternative therapeutic approach for ED, especially in pathologic conditions associated with increased levels of this cytokine.

AB - Introduction. 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-α). Aim. We hypothesized that increased TNF-α levels impair cavernosal function. Methods. In vitro organ bath studies were used to measure cavernosal reactivity in mice infused with vehicle or TNF-α (220 ng/kg/min) for 14 days. Gene expression of nitric oxide synthase isoforms was evaluated by real-time polymerase chain reaction. Main Outcome Measures. Corpora cavernosa from TNF-α-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-α-infused mice displayed decreased nonadrenergic-noncholinergic (NANC)-induced relaxation (59.4 ± 6.2 vs. control: 76.2 ± 4.7; 16Hz) 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-α-infused mice. Additionally, infusion of TNF-α increased cavernosal responses to endothelin-1 and endothelin receptor A subtype (ETA) receptor expression (P < 0.05) and slightly decreased tumor necrosis factor-alpha receptor 1 (TNFR1) expression (P = 0.063). Conclusion. Corpora cavernosa from TNF-α-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-α plays a detrimental role in erectile function. Blockade of TNF-α actions may represent an alternative therapeutic approach for ED, especially in pathologic conditions associated with increased levels of this cytokine.

KW - Corpus cavernosum

KW - Endothelial nitric oxide synthase

KW - Mouse

KW - Neuronal nitric oxide synthase

KW - Tumor necrosis factor-alpha

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