Nitric oxide is a gaseous signaling molecule that cells produce to communicate with one another. It easily diffuses across cell membranes, making it an effective messenger for both nearby and internal cellular functions. As a gasotransmitter, nitric oxide is involved in a vast array of physiological processes, including the operation of the nervous system, the immune response, and the regulation of the cardiovascular system.
The Role of Nitric Oxide Synthase Enzymes
The body’s primary method for producing nitric oxide relies on enzymes known as nitric oxide synthases (NOS). These enzymes facilitate a chemical reaction that transforms the amino acid L-arginine into nitric oxide and L-citrulline. This complex reaction requires other molecules to function, including oxygen and specific cofactors like NADPH.
There are three main isoforms of NOS enzymes, each with a distinct location and function. The first is endothelial NOS (eNOS), which resides in the endothelium, the thin layer of cells lining blood vessels. Here, eNOS produces nitric oxide to regulate vascular function and maintain blood flow. The continuous, low-level release of nitric oxide by eNOS supports cardiovascular health.
A second isoform, neuronal NOS (nNOS), is primarily found in the central and peripheral nervous systems. Through nNOS, nerve cells synthesize nitric oxide to act as a neurotransmitter, a chemical messenger that allows neurons to communicate. This form of nitric oxide is involved in processes ranging from memory formation to the regulation of blood flow in the brain.
The third isoform is inducible NOS (iNOS), a component of the immune system. Unlike eNOS and nNOS that are active at low levels, iNOS is “inducible,” meaning its production is ramped up in response to triggers like invading bacteria or inflammatory signals. The large amounts of nitric oxide generated by iNOS act as a defense mechanism against pathogens.
An Alternative Route Through Diet
Beyond enzymatic production, nitric oxide can be generated through a pathway that begins with diet. This alternative route, the nitrate-nitrite-nitric oxide pathway, is not dependent on NOS enzymes. It utilizes dietary nitrates as the starting material for nitric oxide synthesis.
The process begins with eating nitrate-rich foods, such as leafy green vegetables like spinach and arugula, and root vegetables like beetroot. These dietary nitrates are absorbed in the small intestine and enter the bloodstream. A significant portion of the circulating nitrate is then taken up by the salivary glands and concentrated in saliva.
The next step occurs in the mouth, where bacteria on the tongue’s surface convert the nitrate in saliva into nitrite. This nitrite-rich saliva is then swallowed, traveling to the stomach. In the acidic environment of the stomach, the nitrite is chemically reduced into nitric oxide.
This dietary pathway’s effectiveness is linked to the composition of the oral microbiome. It functions as a complementary system to the L-arginine-based synthesis, becoming particularly active under conditions of low oxygen.
Factors That Influence Synthesis Rates
Several factors can modulate the efficiency of nitric oxide synthesis. Physical activity, for instance, has a pronounced effect on production. Aerobic exercise, such as running or swimming, stimulates blood flow, which activates eNOS in the lining of blood vessels, leading to greater nitric oxide generation and improved vascular function.
Diet quality also plays a role beyond simply providing nitrates. Antioxidants, like vitamin C and polyphenols, can help protect nitric oxide from being broken down by free radicals, increasing its bioavailability. The NOS enzymes also require specific cofactors to function correctly, and a nutrient-rich diet supports the availability of these components.
The body’s ability to produce nitric oxide naturally declines with age, as the eNOS pathway becomes less efficient over time. This age-related decrease in enzymatic production makes the dietary pathway an increasingly important contributor to maintaining nitric oxide levels in older adults.
Sunlight is another environmental factor that can influence nitric oxide levels. Exposure of the skin to UV light can trigger the release of nitric oxide from pre-existing stores within skin cells into the bloodstream. This mechanism is distinct from the primary synthesis pathways.