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.
- Corpus cavernosum
- Endothelial nitric oxide synthase
- Neuronal nitric oxide synthase
- Tumor necrosis factor-alpha
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology