Nitric Oxide: The Key to Healthy Hearts and Open Arteries
By Joshua Helman, MD
If you were to imagine your body as a busy city, the cardiovascular system would be the highways and network of roads and streets. Your heart would be the central hub that pumps blood throughout the body, the same way traffic flows through the city’s center. Your arteries and veins act as the roads that deliver oxygen-rich blood to every corner.
Just as traffic signals regulate the flow of vehicles, the cardiovascular system maintains proper blood pressure and circulation to ensure efficient delivery of nutrients and oxygen to tissues and organs. Any disruption in this system, such as a blockage or obstruction, will cause a traffic jam, affecting the smooth movement of vital resources and potentially leading to health problems.
With this significant role, it is important to make sure there’s integrity of the highways and roads, just like you need to take care of your brain and body. This is where your endothelium comes into play!
The endothelium is a thin layer of cells that lines the interior surface of blood vessels and lymphatic vessels.1 It regulates vascular tone, blood flow, and the interaction of blood with the vessel wall. It plays a key role in keeping your blood moving smoothly by controlling the contraction and relaxation of your blood vessels. In addition, a healthy endothelium maintains a perfect balance of allowing the passage of fluids between its cells to nourish tissues while simultaneously forming a resilient barrier to safeguard the blood from harmful substances.
The structure of the endothelium, consisting of endothelial cells and the basal lamina, contributes to its function. Endothelial cells have mechanoreceptors that allow them to sense shear stress because of the flow of blood, enabling the blood vessel to adapt its diameter and wall thickness to suit the blood flow. They also mediate rapid responses to neural signals for blood vessel dilation by releasing nitric oxide (NO) to make smooth muscle relax in the vessel wall.1
As time passes, highways and roads become worn out, and the same happens with your endothelium. The endothelium can become rigid because of different factors, including altered mechanical forces such as shear stress, stretch, and stiffness, which can happen during the onset of a disease. This event influences endothelial cell behavior and contributes to pathological changes.
Ultimately, our endothelium becomes rigid when the production of NO decreases. Nitric oxide plays a huge role in maintaining the integrity and flexibility of your endothelium.
NO is synthesized in the vascular endothelium from the substrate L-arginine in a reaction catalyzed by endothelial nitric oxide synthase. This process allows the endothelium to mediate rapid responses to neural signals for blood vessel dilation. When neural signals trigger the release of NO from the endothelium, NO diffuses into the underlying smooth muscle cells of the vessel wall, where it activates the enzyme guanylate cyclase. This activation leads to the production of cyclic guanosine monophosphate (cGMP), which in turn causes the relaxation of the smooth muscle, leading to vasodilation.2,3
With nitric oxide’s significant role in your cardiovascular health, what happens when there is impaired bioavailability of this molecule?
According to studies, reduced release or availability of NO results in impaired endothelium-dependent vascular relaxation, contributing to endothelial dysfunction. This condition is characterized by disrupted vascular and increased inflammatory reactions within the blood vessel wall. This impairs vascular homeostasis, leading to reduced antioxidant and anti-inflammatory effects and increased prothrombotic and proinflammatory effects. In addition, this condition is associated with the development and progression of various cardiovascular diseases, including hypertension, diabetes, and atherosclerosis.4
Generally, the body can produce sufficient bioavailable nitric oxide in our 20s and 30s, but our ability to produce NO naturally diminishes as we age. Lifestyle choices such as consuming processed food and exposure to environmental toxins and pollution also contribute to the reduction of NO.
The key is to regulate NO bioavailability because both the lack and excess of this molecule can have various important implications for your cardiovascular health. There are different ways to regulate nitric oxide production in the body:
Dietary factors: Certain dietary factors can regulate NO production, such as dietary protein, L-arginine, and polyunsaturated fatty acids. Foods high in nitrates, such as leafy greens and beets, can also promote NO production.5
Exercise: Regular physical activity, including both aerobic and anaerobic exercise, has been shown to increase endothelial NO production and improve vascular function.6
Supplementation: Several dietary supplements have been shown to contribute to NO synthesis and levels. L-arginine and L-citrulline are two amino acids directly involved in NO synthesis, and their supplementation has been found to increase NO levels. L-arginine is a precursor to NO synthesis, while L-citrulline acts as an L-arginine precursor that is further converted to NO.7 Cardio Miracle is a favorite support as well.
NO-releasing technologies: Ongoing research is focused on developing technologies that can safely and effectively release NO in a targeted manner, including the development of NO-releasing compounds and delivery systems for various therapeutic applications.6
Nitric oxide is a simple molecule with complex actions that offer a wide range of biological effects. Its absence and abnormalities have been linked to different cardiovascular conditions. Nitric oxide serves as a pivotal signaling molecule in both cardiac and vascular physiology, holding significant relevance in fundamental medical research, clinical cardiology, and even brain health.
About the Author
Dr. Joshua Helman is a Harvard-trained physician licensed in 14 states. He holds two degrees in biochemistry, a bachelor’s degree (magna cum laude) from Harvard University, and a master’s degree from the University of Cambridge, UK. His medical degree is from Harvard Medical School and MIT. He is board certified by the American Board of Emergency Medicine and the American Board of Lifestyle Medicine. He is the former medical director of Hippocrates Health Institute and has worked at the TrueNorth Health Center with a focus on fasting.
References
Félétou M. The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators. San Rafael (CA): Morgan & Claypool Life Sciences; 2011. Available from: https://www.ncbi.nlm.nih.gov/b...
Vallance P, Hingorani A. Endothelial nitric oxide in humans in health and disease. Int J Exp Pathol. 1999 Dec;80(6):291-303. doi: 10.1046/j.1365-2613.1999.00137.x. PMID: 10632779; PMCID: PMC2517837.
Félétou M. The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators. San Rafael (CA): Morgan & Claypool Life Sciences; 2011. Chapter 4, Endothelium-Dependent Regulation of Vascular Tone. Available from: https://www.ncbi.nlm.nih.gov/b...
Park KH, Park WJ. Endothelial dysfunction: clinical implications in cardiovascular disease and therapeutic approaches. J Korean Med Sci. 2015 Sep;30(9):1213-25. doi: 10.3346/jkms.2015.30.9.1213. Epub 2015 Aug 13. PMID: 26339159; PMCID: PMC4553666.
Luiking YC, Engelen MP, Deutz NE. Regulation of nitric oxide production in health and disease. Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):97-104. doi: 10.1097/MCO.0b013e328332f99d. PMID: 19841582; PMCID: PMC2953417.
Bryan NS. Nitric oxide enhancement strategies. Future Sci OA. 2015 Aug 1;1(1):FSO48. doi: 10.4155/FSO.15.48. PMID: 28031863; PMCID: PMC5137939.
Kiani AK, Bonetti G, Medori MC, Caruso P, Manganotti P, Fioretti F, Nodari S, Connelly ST, Bertelli M. Dietary supplements for improving nitric-oxide synthesis. J Prev Med Hyg. 2022 Oct 17;63(2 Suppl 3):E239-E245. doi: 10.15167/2421-4248/jpmh2022.63.2S3.2766. PMID: 36479475; PMCID: PMC9710401.
