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Article

NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart

  • Authors:
    • Chen Wang
    • Shigang Qiao
    • Lei Hong
    • Jie Sun
    • Tuanjie Che
    • Jianzhong An
    • Amadou K.S. Camara
  • View Affiliations / Copyright

    Affiliations: Institute of Clinical Medicine Research, Suzhou, Jiangsu 215153, P.R. China, Laboratory of Precision Medicine and Translational Medicine, The Affiliated Suzhou Science and Technology Town Hospital of
Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China, Department of Anesthesiology and Physiology,
 Medical College of Wisconsin, Milwaukee, WI 53226, USA
  • Pages: 615-622
    |
    Published online on: December 27, 2019
       https://doi.org/10.3892/ijmm.2019.4445
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Abstract

Anesthetic preconditioning (APC) may decrease the myocardium injury nearly 50% following ischemia/reperfusion (I/R) by enhancing recovery of cardiac function, reducing myocardial enzyme release and lowering infarct size when utilized as pretreatment or posttreatment agents. I/R increases nitric oxide (NO) production through endothelial NO synthase (NOS3) and heat shock protein 90 (HSP90). The present study aimed to observe the role of BH4 availability and the association of HSP90 with NOS3 in APC‑mediated cardioprotection against I/R injury. Isolated rat hearts were subjected to no‑flow ischemia for 30 min and reperfusion for 120 min. Sevoflurane (3.5%) was administered for 15 min followed by a 15 min washout prior to ischemia. 2,4-Diamino-6-hydroxypyrimidine (DAHP) or sepiapterin (SP) was administered for 40 min until the onset of ischemia. The results revealed that compared with pre‑ischemic basal levels, BH4 levels decreased and BH2 levels increased following I/R. BH4 levels were significantly increased and BH2 levels were significantly decreased in the APC + I/R hearts compared with the I/R group hearts. The BH4:BH2 ratio in the APC‑treated hearts was also increased compared with that in the I/R group hearts. SP increased the recovery of contractile function and the production of NO, and decreased the production of superoxide anion (O2·‑) in I/R heart, but did not elicit these effects in APC‑treated hearts. DAHP treatment inhibited the APC‑mediated recovery of contractile function, increased O2·‑ levels and decreased NO production, but had no effect in I/R hearts. The cardioprotection of APC was demonstrated to be modulated by the BH4 precursor SP, which increased BH4 levels, or DAHP, which inhibited GTP cyclohydrolase I. Both APC and SP treatments increased the combination of HSP90 and NOS3, which improved the NOS3 activity and function. The results suggested that BH4, which servesas a cofactor for NOS, mediated the resistance of APC to I/R injury by promoting the binding of HSP90 and NOS3.
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Copy and paste a formatted citation
Spandidos Publications style
Wang C, Qiao S, Hong L, Sun J, Che T, An J and Camara AK: NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart. Int J Mol Med 45: 615-622, 2020.
APA
Wang, C., Qiao, S., Hong, L., Sun, J., Che, T., An, J., & Camara, A.K. (2020). NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart. International Journal of Molecular Medicine, 45, 615-622. https://doi.org/10.3892/ijmm.2019.4445
MLA
Wang, C., Qiao, S., Hong, L., Sun, J., Che, T., An, J., Camara, A. K."NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart". International Journal of Molecular Medicine 45.2 (2020): 615-622.
Chicago
Wang, C., Qiao, S., Hong, L., Sun, J., Che, T., An, J., Camara, A. K."NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart". International Journal of Molecular Medicine 45, no. 2 (2020): 615-622. https://doi.org/10.3892/ijmm.2019.4445
Copy and paste a formatted citation
x
Spandidos Publications style
Wang C, Qiao S, Hong L, Sun J, Che T, An J and Camara AK: NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart. Int J Mol Med 45: 615-622, 2020.
APA
Wang, C., Qiao, S., Hong, L., Sun, J., Che, T., An, J., & Camara, A.K. (2020). NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart. International Journal of Molecular Medicine, 45, 615-622. https://doi.org/10.3892/ijmm.2019.4445
MLA
Wang, C., Qiao, S., Hong, L., Sun, J., Che, T., An, J., Camara, A. K."NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart". International Journal of Molecular Medicine 45.2 (2020): 615-622.
Chicago
Wang, C., Qiao, S., Hong, L., Sun, J., Che, T., An, J., Camara, A. K."NOS cofactor tetrahydrobiopterin contributes to anesthetic preconditioning induced myocardial protection in the isolated ex vivo rat heart". International Journal of Molecular Medicine 45, no. 2 (2020): 615-622. https://doi.org/10.3892/ijmm.2019.4445
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