科研之友
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摘要
Aim: Angiotensin II (AngII), a corpus cavernosum (CC) constrictor peptide, modulates Toll like receptor (TLR) expression, a key element of the innate immune system, contributing to impaired vascular function in pathological conditions. However, it is unknown whether TLR4 is involved in AngII-induced erectile dysfunction. In this study, we investigated whether TLR4 plays a role in cavernosal dysfunction caused by AngII upregulation. Material and methods: Cavernosal smooth muscle cells (CSMC) from C57/BL6 mice were treated with AngII (0.1 mu M) or bacterial LPS (50 ng/ml) for 12-24 h and TLR4 expression was assessed. Mice were infused with AngII (90 ng/min, 28 days) and treated with anti-TLR4 antibody (0.1 mg/daily, i.p.) for the last 14 days of the treatment. CC tissue was used for functional studies and for Western blotting. Nitric Oxide Synthase (NOS) activity was measured by conversion of [H-3]-L-arginine to [3H]-L-citrulline, systemic TNF-alpha levels by ELISA, and reactive oxygen species (ROS) by immunofluorescence. Key findings: We report upregulation of TLR4 in CSMC following AngII or LPS stimulation. In AngII-infused mice, chronic treatment with anti-TLR4 antibody (28 +/- 2.1%) attenuates adrenergic CC contraction, which also ameliorates nitrergic (68.90 +/- 0.21 vs. 51.07 +/- 0.63, 8 Hz, AngII-infused mice treated vs. non-treated). Decreased endothelial NOS expression, reduced NOS activity, and augmented levels of TNF-a, and ROS were found following AngII-infusion. These alterations were prevented, or at least decreased by anti-TLR4 antibody treatment. Significance: Inhibition of TLR4 ameliorates AngII-impaired cavernosal relaxation, decreases TNF-alpha levels, and restores NO bioavailability, demonstrating that TLR4 partly mediates AngII-induced cavernosal dysfunction.
- 出版日期2017-12-15
