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A κ-OR Agonist Protects the Endothelial Function Impaired by Hyperuricemia Through Regulating the Akt/eNOS Signal Pathway

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Abstract

To investigate the effects of κ-OR agonist on hyperuricemia rats and injured endothelial function, as well as the underlying mechanism. A hyperuricemia model was established on rats. The endothelial protective effects of U50,488H were evaluated and compared to the controlled groups. The protein levels of eNOS, p-eNOS, Akt, and p-Akt were determined using western blot analysis. ELISA was employed to measure the expression of soluble ET-1, ICAM-1, TNF-α, and NO in cell supernatants and rat serum samples. Cell migration and the artery tension were determined by in vitro functional assays. The suppressed production of ET-1, ICAM-1, and NO in the hyperuricemia rats was promoted by the treatment of U50,488H, which was reversed by the co-administration of nor-BNI. P-eNOS/eNOS and p-Akt/Akt were up-regulated by the incubation of serum from hyperuricemia rats, which was down-regulated by the introduction of U50,488H. The vascular tension of vessels incubated with U50,488H was higher than the baseline in the presence of ACh, which was lower than baseline in the presence of SNAP. U50,488H significantly promoted the release of ET-1, ICAM-1, and NO, and inhibited the release of TNF-α from endothelial cells and the migration ability of neutrophils in the presence of hyperuricemia rat serum, which were reversed by the co-incubation with nor-BNI, Akt inhibitor or L-NAME. U50,488H protected the endothelial function impaired by hyperuricemia through regulating the Akt/eNOS signal pathway.

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Funding

The general fund projects of Sichuan Provincial Department of Education (18ZB0177).

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Authors and Affiliations

  1. Department of Geriatrics, The First Affiliated Hospital of Chengdu Medical College, Sichuan, Chengdu, China

    Qin Zheng

  2. Department of Cardiovascular Medicine, The First Affiliated Hospital of Chengdu Medical College, Sichuan, Chengdu, China

    Hong Yang, Qiuhong Chen, Xiaohui Li & Jingyi Guo

  3. Department of Cardiovascular Medicine, The Second Affiliated Hospital of Chengdu Medical College, Sichuan, China

    Qi Wu

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  1. Qin Zheng
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Correspondence to Qi Wu.

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Qin Zheng and Qi Wu contributed equally to this work.

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Zheng, Q., Wu, Q., Yang, H. et al. A κ-OR Agonist Protects the Endothelial Function Impaired by Hyperuricemia Through Regulating the Akt/eNOS Signal Pathway. Probiotics & Antimicro. Prot. 14, 751–759 (2022). https://doi.org/10.1007/s12602-022-09945-1

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