Surreal illustration of nitric oxide molecule.

Nitric Oxide: Unlocking the Secrets of a Molecular Messenger

Mira Elwood in Health & Wellness January 2026 • 4 min read.

"From atmospheric pollutant to Nobel Prize-winning discovery, explore the fascinating journey of nitric oxide and its vital role in health."

In 1998, the Nobel Prize in Physiology or Medicine was awarded to Robert Furchgott, Louis Ignarro, and Ferid Murad for their revolutionary discoveries about nitric oxide (NO). Before this recognition, NO was primarily known as a toxic pollutant gas, a far cry from its now-established role as a crucial signaling molecule within the body.

The initial skepticism surrounding NO's biological role stemmed from its chemical properties. It's highly lipid-soluble, allowing it to freely cross cell membranes. As a free radical, it readily reacts with oxygen, other radicals, and various chemical species. Initially, these characteristics seemed to preclude its existence and function as a signaling molecule within the body.

However, groundbreaking research revealed that mammalian tissues produce NO, sparking an explosion of studies that unequivocally demonstrated the physiological significance of the NO-cyclic GMP pathway. This pathway is fundamental to numerous biological processes, and ironically, the very properties that once argued against NO's role have proven essential to its function.

The Accidental Discovery: How NO Research Began

Surreal illustration of nitric oxide molecule.

The earliest experiments that directly explored nitric oxide's effects were led by Ferid Murad in 1977. Murad discovered that nitric oxide gas could activate the cytosolic isoform of guanylyl cyclase (GC). This enzyme then catalyzes the conversion of GTP to cyclic GMP, a crucial signaling molecule.

Murad's interest in NO's effects on guanylyl cyclase was sparked by a seemingly mundane problem. Bacterial contamination often disrupted his enzyme protein solutions. To combat this, he added sodium azide (NaN3), an antibacterial agent, to unpurified GC preparations. Surprisingly, this increased the enzyme's catalytic activity by nearly 100-fold. He noticed also that the addition of NaN3 to isolated tissue preparations caused a marked increase in cyclic GMP levels.

The Role of Sodium Azide: Sodium azide, in the presence of catalase, was found to convert to NO. This accounted for the markedly higher GC activity and increased tissue levels of cyclic GMP.
Launching a Field: These experiments with NaN3 and NO essentially launched the field of NO research.

These accidental yet pivotal discoveries opened the door to understanding NO's role in vasodilation, platelet aggregation, and neurotransmission. The work of Furchgott, Ignarro, and Murad demonstrated how this simple molecule could have far-reaching effects on human health.

The Future of NO Research: What's Next?

The journey of nitric oxide research is far from over. As we celebrate the 20th anniversary of the Nobel Prize, it's clear that there are still many exciting avenues to explore. From understanding its role in cancer therapy to harnessing its potential in treating heart failure, NO continues to be a molecule of immense therapeutic promise. The ongoing exploration of nitric oxide's properties and interactions promises to unlock even more innovative strategies for improving human health.

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Everything You Need To Know

How did the perception of nitric oxide (NO) change from a pollutant to a vital molecule?

Nitric oxide (NO) was initially dismissed as a toxic pollutant. However, research revealed it is a crucial signaling molecule involved in numerous biological processes. Its ability to freely cross cell membranes and react with various chemical species, once seen as limitations, are now understood to be essential to its function. The discovery of the NO-cyclic GMP pathway highlighted its physiological significance, leading to a deeper understanding of its role in the body.

What was Ferid Murad's key experiment that revealed nitric oxide's effect on guanylyl cyclase (GC)?

Ferid Murad's work in 1977 demonstrated that nitric oxide gas could activate the cytosolic isoform of guanylyl cyclase (GC). This activation leads to the conversion of GTP to cyclic GMP, a critical signaling molecule. This discovery stemmed from his experiments using sodium azide (NaN3) to combat bacterial contamination in enzyme protein solutions, which unexpectedly increased the enzyme's catalytic activity and cyclic GMP levels in tissue preparations. Sodium azide converts to NO in the presence of catalase, revealing NO's role in these processes.

What are the potential implications of nitric oxide's role in vasodilation, platelet aggregation, and neurotransmission?

The accidental discovery of nitric oxide's effects on vasodilation, platelet aggregation, and neurotransmission has significant implications for cardiovascular health and neurological function. Further research into these areas could lead to new treatments for conditions like hypertension, stroke, and neurodegenerative diseases. The NO-cyclic GMP pathway plays a crucial role in these processes, making it a key target for therapeutic interventions. By manipulating this pathway, scientists aim to develop targeted therapies that can improve patient outcomes.

What are the current research directions for utilizing nitric oxide in cancer therapy and heart failure treatment?

Current research is focused on harnessing the potential of nitric oxide in cancer therapy and treating heart failure. Understanding how nitric oxide interacts with cancer cells and the cardiovascular system could lead to innovative approaches for preventing and treating these diseases. Ongoing studies aim to identify specific targets within the NO-cyclic GMP pathway that can be manipulated to achieve therapeutic benefits. This includes exploring the use of NO-releasing drugs, gene therapies, and other strategies to enhance or inhibit NO signaling in specific tissues and cells.

Why was the Nobel Prize awarded for discoveries related to nitric oxide (NO), and what does this recognition signify for future research?

The Nobel Prize in Physiology or Medicine was awarded to Robert Furchgott, Louis Ignarro, and Ferid Murad in 1998 for their discoveries regarding nitric oxide (NO) as a signaling molecule in the cardiovascular system. The properties of nitric oxide are vital to a number of key processes. Further research into nitric oxide's properties and interactions may unlock innovative strategies for improving human health, offering new possibilities for the development of targeted therapies.