Why Humans Are Prone to Coronary Artery Disease – Part 3

Why Humans Are Prone to Coronary Artery Disease – Part 3

Nitric Oxide: The Molecule of Circulatory Life

Prepared by Dr. Michael Garko, Ph.D., M.S., M.A.

 

When it comes to cardiovascular health, one molecule has quietly transformed our understanding of how arteries stay healthy and flexible: nitric oxide (NO). Discovered in the late 20th century and honored with the 1998 Nobel Prize in Physiology or Medicine, NO is a gas that acts as a master regulator of vascular health (Ignarro et al., 1999). Yet, despite its importance, many people unknowingly live with declining NO levels, a silent shift that increases their risk of coronary artery disease (CAD).

In this installment, we explore how NO works, why its production declines with age and modern lifestyles, and what science suggests you can do to restore it.

The Body’s Natural Vasodilator

Nitric oxide is produced by endothelial cells, the single-cell-thick lining inside our blood vessels, using an enzyme called endothelial nitric oxide synthase (eNOS). Once released, NO signals the smooth muscle cells in artery walls to relax, causing vasodilation, which is the widening of blood vessels, thereby improving blood flow and reducing pressure on arterial walls (Moncada & Higgs, 2006).

Beyond improving circulation, NO plays a multifaceted protective role:

  • Reduces platelet aggregation and clot formation, lowering the risk of blockages.

  • Suppresses vascular inflammation, a key driver of atherosclerosis (Förstermann & Sessa, 2012).

  • Inhibits smooth muscle overgrowth, preventing arteries from stiffening.

  • Enhances oxygen delivery to tissues, improving heart, brain, and muscle performance.

Without enough NO, arteries become less responsive and more prone to damage — creating the perfect environment for plaque buildup and CAD progression.

Why Nitric Oxide Declines with Age

By the time we reach age 40, NO production naturally declines by nearly 50%, and by age 60, levels may drop to just 20–30% of youthful capacity (Seals et al., 2011). Several factors drive this decline:

  1. Endothelial Dysfunction – Damage from high blood pressure, oxidized LDL, hyperglycemia, and smoking impairs the endothelium’s ability to produce NO (Gimbrone & García-Cardeña, 2016).

  2. Oxidative Stress – Excess free radicals destroy NO before it can act, a process accelerated by poor diet, pollutants, and chronic stress (Lundberg et al., 2008).

  3. Arginine and Nitrate Pathway Disruptions – NO is made from the amino acid L-arginine and dietary nitrates. Deficiencies or enzyme dysfunctions limit its synthesis (Bryan & Loscalzo, 2017).

  4. Sedentary Lifestyle – Physical inactivity reduces eNOS expression, lowering NO output (Green et al., 2017).

This combination creates a vicious cycle: declining NO weakens vascular defenses, enabling inflammation and oxidative damage, which further suppress NO, a cascade that accelerates CAD risk.

Nitric Oxide, CAD, and the Inflammatory Connection

Low NO levels contribute directly to endothelial dysfunction, one of the earliest events in atherosclerosis. Without NO:

  • Arteries lose their natural ability to dilate, forcing the heart to pump harder.

  • Platelets stick more easily, increasing clot risk.

  • Inflammation escalates, inviting immune cells that promote plaque growth.

This is why studies consistently link NO depletion to hypertension, arterial stiffness, and increased CAD incidence (Tousoulis et al., 2012). Conversely, restoring NO bioavailability improves vascular tone and slows plaque progression (Lundberg et al., 2018).

Supporting Healthy Nitric Oxide Levels

Science shows that diet, lifestyle, and botanicals can dramatically enhance NO production and protect endothelial function:

  • Nitrate-Rich Foods — Beets, spinach, arugula, and other leafy greens provide dietary nitrates that convert to NO in the body (Kapil et al., 2015).

  • Polyphenol-Rich Botanicals — Compounds in hawthorn, aged garlic extract, green tea, and dark berries enhance eNOS activity and improve NO bioavailability (Ried et al., 2016; Tadić et al., 2021).

  • Exercise — Even moderate aerobic activity stimulates eNOS expression, boosting NO production and vessel responsiveness (Green et al., 2017).

  • Omega-3 Fatty Acids — Found in fatty fish and flaxseeds, they improve endothelial health and promote NO synthesis (Mori & Woodman, 2006).

  • Reducing Oxidative Stress — Diets rich in antioxidants (berries, olive oil, nuts) protect NO from premature breakdown.

Conclusion: Nitric Oxide at the Heart of Vascular Health

Nitric oxide (NO) sits at the center of circulatory health, acting as a natural vasodilator, anti-inflammatory agent, and vascular protector. As explored in this article, NO maintains arterial flexibility, suppresses clot formation, reduces oxidative stress, and ensures healthy oxygen delivery throughout the body (Förstermann & Sessa, 2012).

Yet, modern life marked by aging, poor diet, chronic stress, sedentary habits, and oxidative overload steadily diminishes NO production (Seals et al., 2011). This decline sets the stage for endothelial dysfunction, plaque formation, and ultimately, coronary artery disease. The good news is that science offers effective strategies to restore NO bioavailability: consuming nitrate-rich vegetables, adopting polyphenol-rich botanicals, exercising regularly, and reducing oxidative stress all support healthy NO levels (Kapil et al., 2015; Green et al., 2017).



Looking Ahead

Nitric oxide is not just a molecule. It’s the lifeblood of vascular health. By keeping arteries flexible, calming inflammation, and optimizing oxygen delivery, NO sits at the crossroads of circulation, immunity, and longevity.

In Part 4, we’ll examine another hidden driver of cardiovascular disease: chronic stress and its profound effects on circulation, heart rhythm, and inflammatory balance. Understanding these connections equips us to protect our arteries and our future.

References

  • Bryan, N. S., & Loscalzo, J. (2017). Nitric oxide and cardiovascular health. Springer.

  • Förstermann, U., & Sessa, W. C. (2012). Nitric oxide and endothelial dysfunction. European Heart Journal, 33(7), 829–837. https://doi.org/10.1093/eurheartj/ehr304

  • Gimbrone, M. A., & García-Cardeña, G. (2016). Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circulation Research, 118(4), 620–636. https://doi.org/10.1161/CIRCRESAHA.115.306301

  • Green, D. J., et al. (2017). Exercise-induced improvements in vascular function: NO and eNOS upregulation. Journal of Applied Physiology, 123(3), 975–984. https://doi.org/10.1152/japplphysiol.00065.2017

  • Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1999). Endothelium-derived relaxing factor: Discovery and function. Journal of Physiology, 516(1), 263–284. https://doi.org/10.1111/j.1469-7793.1999.263bb.x

  • Kapil, V., et al. (2015). Dietary nitrate provides sustained blood pressure lowering in hypertensive patients. Hypertension, 65(2), 320–327. https://doi.org/10.1161/HYPERTENSIONAHA.114.04675

  • Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery, 7(2), 156–167. https://doi.org/10.1038/nrd2466

  • Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2018). Strategies to enhance NO bioavailability. Nature Reviews Cardiology, 15(6), 377–394. https://doi.org/10.1038/s41569-018-0008-z

  • Mori, T. A., & Woodman, R. J. (2006). Omega-3 fatty acids and endothelial function. Clinical Science, 111(1), 1–10. https://doi.org/10.1042/CS20060037

  • Ried, K., Fakler, P., & Stocks, N. P. (2016). Effect of aged garlic extract on endothelial function and cardiovascular risk factors. Nutrition Reviews, 74(12), 803–814. https://doi.org/10.1093/nutrit/nuw036

  • Seals, D. R., Jablonski, K. L., & Donato, A. J. (2011). Aging and vascular endothelial function. Journal of Physiology, 589(Pt 21), 5075–5084. https://doi.org/10.1113/jphysiol.2011.211219

  • Tadić, P. P., & Singh, S. K. (2021). Hawthorn: Cardioprotective herb with bioactive compounds. Frontiers in Pharmacology, 12, 641705. https://doi.org/10.3389/fphar.2021.641705

  • Tousoulis, D., et al. (2012). The role of nitric oxide in coronary artery disease. Current Vascular Pharmacology, 10(1), 4–18. https://doi.org/10.2174/157016112798829832

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