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Nitric Oxide, Its Role in Diabetes Mellitus and Methods to Improve Endothelial Function

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Diabetes and Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Vascular disease plays a critical role in morbidity and mortality associated with diabetes mellitus. Nitric oxide is an essential molecule involved in vascular homeostasis. It is generated by the family of enzymes known as NO synthases, which include endothelial NOS (eNOS), neuronal NOS (nNOS), and cytokine-inducible NOS (iNOS). NO effects include maintenance of resting vascular tone, production and release of other vasodilator substances responsible for endothelial-dependent vasodilation, modulation of expression of endothelial vasoconstrictors and growth factors, maintaining integrity of the vascular endothelium through platelet and leukocyte interaction with the vessel wall. Besides its positive effects, NO also contributes to the atherosclerotic plaque formation in certain circumstances.

Numerous studies have demonstrated an important role of NO in the pathogenesis of diabetic vascular complications. The proposed mechanisms by which diabetes affects endothelial function include changes in glucose metabolism, alterations in insulin signaling pathways, impaired NO synthesis due to oxidative stress, decreased availability of substrates and cofactors of NO synthesis, eNOS modifications causing its uncoupling, leading to superoxide generation and peroxynitrite formation, presence of endogenous eNOS inhibitors, and increased NO breakdown. Diabetes comorbidities, including hypertension and dyslipidemia, further exacerbate vascular dysfunction in diabetes. Despite in vitro and in vivo experiments suggesting that certain substances (e.g., vitamins C and E, tetrahydrobiopterin, l-arginine, estrogens) can cause improvement in endothelial function, the data demonstrating their clinical effectiveness is lacking. On the other hand, certain known medications (ACEi, ARBs, statins, many diabetes medications) have known positive effect on endothelial function and improve outcomes in diabetic patients. Knowing mechanisms of NO metabolism in diabetes allows to find new therapeutic targets for reversal of endothelial dysfunction and improvement in clinical outcomes.

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  1. Department of Medicine, Steward St. Elizabeth’s Medical Center, Boston, MA, USA

    Mariia Nikolaeva

  2. Steward St. Elizabeth’s Medical Center, Tufts University Medical School, Brighton, MA, USA

    Michael Johnstone

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    Michael Johnstone

  2. Beth Israel Deaconess Medical Center / Harvard Medical School, Boston, MA, USA

    Aristidis Veves

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Nikolaeva, M., Johnstone, M. (2023). Nitric Oxide, Its Role in Diabetes Mellitus and Methods to Improve Endothelial Function. In: Johnstone, M., Veves, A. (eds) Diabetes and Cardiovascular Disease. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-13177-6_7

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