From diabetes to hypertension, cancer to drug addiction, stroke to intestinal motility, memory and learning disorders to septic shock, sunburn to anorexia, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Only within the last 25 years was Nitric Oxide discovered as a product of enzymatic synthesis in mammals, there are more than 114,000 scientific papers dealing with this remarkable molecule with most of these published within the last eight years.
Nitric oxide or NO has become one of the most studied molecules in the scientific and medical literature. Although only relatively recently was it discovered to be produced in the human body, the chemical properties of NO gas were first characterized in 1772. Indeed, there have been over 140,000 publications on NO, more than half of which have appeared in the last 12 years. NO produced in biological systems has a half-life of less than 1 second and is biologically active in the concentration range from 1-100nM. Another interesting feature is that NO is lipophilic so that it can readily permeate biological membranes. The concept of a gas selectively and specifically mediating cell signalling events is unlike the conventional receptor ligand concepts associated with cell signalling.
These discoveries were so revolutionary that the 1998 Nobel Prize in Physiology or Medicine was awarded to Robert Furchgott, Louis Ignarro, and Ferid Murad, for their discoveries of NO as a signal molecule in the vasculature and specifically in the control of blood pressure. In addition to this role, NO is one of the most important signalling molecules in the body, and is involved in virtually every organ system where it is responsible for modulating an astonishing variety of effects. NO has been shown to be involved in and affect (just to list a few major examples) neurotransmission, memory, stroke, glaucoma and neural degeneration, pulmonary hypertension, penile erection, angiogenesis, wound healing, atherogenesis, inflammation such as arthritis, nephritis, colitis, autoimmune diseases (diabetes, inflammatory bowel disease), invading pathogens, tumors, asthma, tissue transplantation, septic shock, platelet aggregation and blood coagulation, sickle cell disease, gastrointestinal motility, hormone secretion, gene regulation, hemoglobin delivery of oxygen, insulin signalling and diabetes, stem cell proliferation and differentiation, and bronchodilation. One can then begin to appreciate then the many consequences of the loss of the production of nitric oxide.
There have been many discoveries and innovations in the nitric oxide field with regards to diagnostics and therapeutics. We now have an appreciation for how the body makes NO, what goes wrong in patients or subjects that can’t make NO and through emerging science and research are beginning to understand how to therapeutically fix the underlying problems of NO deficiency. Although NO is widely recognized and appreciated in the scientific and medical community, there is still very little awareness around NO by patients and consumers.
Cardiovascular disease – nitric oxide is the most important molecules produced in our cardiovascular system. In fact, loss of the production of nitric oxide is recognized as one of the earliest events in the onset and progression of cardiovascular disease. From high blood pressure, heart failure, coronary artery disease, atherosclerosis, heart attack and stroke, nitric oxide play an essential role in combatting all these conditions.
Immune function – when our body is invaded by pathogens such as bacteria, viruses, parasites or fungi.
Cancer – nitric oxide appears to play a dual role in cancer. Low, physiological levels of NO appear to have anti-cancer properties whereas higher concentrations produced for prolonged periods may contribute to cancer cell growth and proliferation. There is much focus and current research on understanding how NO affects cancer cell growth.
Immune system responds by producing massive amounts of nitric oxide acutely to kill these pathogens. The production and regulation of nitric oxide by our immune system can help keep us free from any chronic infections.
Nervous system – nitric oxide is a cell signalling molecule and facilitates communication between cells. In the nervous system, nitric oxide is a neurotransmitter involved in long term memory and cognition. Disruption of nitric oxide plays a role in many neurodegenerative diseases such as Alzheimers and Parkinson Disease.
Physical performance – your ability to generate nitric oxide may predict how well you perform athletically. Nitric oxide not only controls and regulates blood flow to working skeletal and heart muscles, but also controls how efficiently your mitochondria generate cellular energy from oxygen. Exercise intolerance in older individuals is due to these people being unable to effectively produce nitric oxide and regulate blood flow to the body.
