Nitric Oxide Signaling in Vascular Physiology
Summary
Nitric oxide (NO) is a gaseous messenger that orchestrates vascular tone, blood flow and endothelial homeostasis. Synthesised predominantly by endothelial nitric oxide synthase (eNOS) in response to shear stress and receptor stimulation, NO diffuses into adjacent smooth muscle cells to activate soluble guanylate cyclase and elevate cyclic guanosine monophosphate (cGMP). This cascade induces vasorelaxation, inhibits platelet aggregation and suppresses leukocyte adhesion, thereby protecting against atherogenesis and hypertension. Beyond its classical vasodilator role, NO interacts with redox-sensitive thiols to regulate protein function via S-nitrosylation and can be converted to nitroxyl (HNO), a related species with unique vasoprotective properties. Dietary nitrate and nitrite serve as complementary sources of NO, particularly under hypoxic conditions, with oral and gut microbiota contributing to their step-wise reduction back to NO. Dysregulation of NO bioavailability underpins many vascular disorders, including endothelial dysfunction, arterial stiffness and microvascular rarefaction. Therapeutic strategies aimed at enhancing NO signalling encompass phosphodiesterase inhibitors, NO donors, dietary interventions and novel HNO-releasing compounds. Emerging insights into the interplay between redox programming, microbiome-mediated nitrate metabolism and NO-driven epigenetic modulation promise to inform personalised approaches for the prevention and treatment of cardiovascular disease.
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Nitric Oxide Signaling in Vascular Physiology publication trend
The graph below shows the total number of articles in nitric oxide signaling in vascular physiology across all publications each year (not limited to Nature Index journals).
Technical terms
Endothelial nitric oxide synthase (eNOS): enzyme in endothelial cells catalysing NO production from L-arginine.
Cyclic guanosine monophosphate (cGMP): intracellular messenger generated by soluble guanylate cyclase upon NO binding, inducing smooth muscle relaxation.
Flow-mediated dilation (FMD): ultrasound-based measure of endothelium-dependent vasodilation reflecting vascular health.
Redox switch: reversible oxidation–reduction modification in signalling proteins that modulates vascular tone.
Nitroxyl (HNO): one-electron reduced form of NO with distinct biological reactivity, emerging as a potential vasoprotective agent.
References
- Flipping Off and On the Redox Switch in the Microcirculation. Annual Review of Physiology (2023).
- Nitric oxide signaling in health and disease. Cell (2022).
- Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study 1–3. American Journal of Clinical Nutrition (2015).
- Nitrate Reduction to Nitrite, Nitric Oxide and Ammonia by Gut Bacteria under Physiological Conditions. PLOS ONE (2015).
- Metagenomic Analysis of Nitrate-Reducing Bacteria in the Oral Cavity: Implications for Nitric Oxide Homeostasis. PLOS ONE (2014).
- Regulation of Protein Function and Signaling by Reversible Cysteine S-Nitrosylation*. Journal of Biological Chemistry (2013).
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