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Endothelial nitric oxide synthase in the microcirculation

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Abstract

Endothelial nitric oxide synthase (eNOS, NOS3) is responsible for producing nitric oxide (NO)—a key molecule that can directly (or indirectly) act as a vasodilator and anti-inflammatory mediator. In this review, we examine the structural effects of regulation of the eNOS enzyme, including post-translational modifications and subcellular localization. After production, NO diffuses to surrounding cells with a variety of effects. We focus on the physiological role of NO and NO-derived molecules, including microvascular effects on vessel tone and immune response. Regulation of eNOS and NO action is complicated; we address endogenous and exogenous mechanisms of NO regulation with a discussion of pharmacological agents used in clinical and laboratory settings and a proposed role for eNOS in circulating red blood cells.

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Acknowledgments

This work was supported by National Institutes of Health Grants HL088554 (BEI), HL107963 (BEI). The American Heart Association provided predoctoral (LAB) and postdoctoral (JTB) fellowships that supported this work. JTB was supported by a National Institutes of Health training Grant (HL007284). Support was also provided by the National Natural Science Foundation of China (XS; 81072063) and China Scholarship Council (XS; 201408210085).

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    1. College of Pharmacy, Dalian Medical University, Dalian, 116044, China

      Xiaohong Shu

    2. Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, P.O. Box 801394, Charlottesville, VA, 22908, USA

      Xiaohong Shu, T. C. Stevenson Keller IV, Daniela Begandt, Joshua T. Butcher, Lauren Biwer, Alexander S. Keller & Brant E. Isakson

    3. Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, USA

      T. C. Stevenson Keller IV, Lauren Biwer & Brant E. Isakson

    4. Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, USA

      Alexander S. Keller

    5. Department of Chemistry, University of Virginia, Charlottesville, USA

      Linda Columbus

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    X. Shu and T. C. Stevenson Keller IV contributed equally to this work.

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    Shu, X., Keller, T.C.S., Begandt, D. et al. Endothelial nitric oxide synthase in the microcirculation. Cell. Mol. Life Sci. 72, 4561–4575 (2015). https://doi.org/10.1007/s00018-015-2021-0

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