By Louis J. Ignarro, PhD
In 1998, I was awarded the Nobel Prize in Physiology or Medicine for my pioneering studies on cardiovascular function and erectile function. We discovered that our bodies produce a small molecule that protects us against hypertension, heart attack and stroke. This same molecule serves as the neurotransmitter released from the nerves that cause penile erection and sexual arousal. The name of the molecule is “nitric oxide,” not to be confused with nitrous oxide (laughing gas), which has totally different properties.
Nitric oxide, also termed NO, is a gaseous molecule that is produced by our arteries in all organs to regulate cardiovascular function. NO causes the muscle cells (smooth muscle) enveloping arteries to relax, thereby causing vasodilation or widening of the arteries. This physiological action results in a decrease in blood pressure within the arteries and increased blood flow to all organs through the dilated arteries. In the erectile tissue, the NO released during sexual stimulation causes profound relaxation or dilation of the arteries within the erectile tissue, termed the corpus cavernosum. This results in engorgement with blood and consequent penile erection.
But not only vascular smooth muscle is relaxed by NO. Nonvascular smooth muscle such as airway smooth muscle in the trachea and bronchioles of the lungs is also relaxed by NO. Advantage was taken of this bronchodilator action of NO in the lungs by Warren Zapol, MD from the Massachusetts General Hospital in Boston, who discovered that inhalation of very small amounts of NO by newborn babies with persistent pulmonary hypertension (constricted pulmonary arteries), results in a dramatic and permanent reversal of hypertension. Inhaled NO (INO) literally turned blue babies into pink babies. Without INO, most babies would have died while others would have required highly invasive procedures to oxygenate their lungs, and may not have survived.
Nitric oxide turns out to be a ubiquitous molecule with many different properties. For example, not only does NO relax smooth muscle, but NO also reacts chemically with certain other molecules in cells to alter their function. The NO produced by our own cells can interact with molecules in invading cells such as bacteria, parasites and viruses to kill them or inhibit their replication or spread. NO has been shown to increase the survival rate of mammalian cells infected with SARS-CoV (Severe Acute Respiratory Syndrome caused by coronavirus). Importantly, in a limited study in 2004, inhaled NO (INO) was demonstrated to be effective against the SARS-CoV in severely ill patients with pneumonia. The mechanism of action was thought to be pulmonary vasodilation and consequent improved oxygenation in the blood of the lungs, thereby killing the virus, which does not do well in a high oxygen environment. In addition, however, I would offer the opinion that the NO also interacts with the virus to kill it directly.
In view of the above knowledge gained by treating SARS CoV patients with INO, it is scientifically logical that INO might be effective in patients with the current SARS CoV-2, or simply, COVID-19, infection. Indeed, a clinical trial of inhaled nitric oxide (INO) in patients with moderate to severe COVID-19 with pneumonia recently received IRB (Institutional Review Board) approval at the Massachusetts General Hospital. Warren Zapol, MD, is director of this project. In the successful treatment of persistent pulmonary hypertension in newborns, the amount of NO inhaled is generally one ppm (part per million). In the clinical trial using COVID-19 patients, the amount of NO will be 100-fold higher, namely, 100 ppm. This is a safe dose of INO, which could prove to be effective in killing the virus and allowing recovery of the patient.
One thing I urge everyone to practice during this coronavirus pandemic is to breathe or inhale through your NOSE and exhale through your mouth. The cells and tissues in the nose, but not the mouth, constantly and continuously produce nitric oxide, which is a gas. The physiological significance of this is that nasally-derived NO improves oxygen delivery into the lungs by causing bronchodilation. Moreover, when inhaling through the nose, your nasal nitric oxide is inhaled into your lungs, where it stands a chance of meeting up with the virus particles. Inhaling through your mouth will NOT accomplish this. By the same token, exhaling through your nose is highly wasteful in that you would be expelling the NO away from the lungs, where it is needed most.
“INHALE THROUGH YOUR NOSE, AND EXHALE THROUGH YOUR MOUTH!”
Dr. Louis J. Ignarro was co-recipient of the 1998 Nobel Prize in Physiology or Medicine together with Dr. Robert F. Furchgott and Dr. Ferid Murad for demonstrating the biochemical formation, actions and signaling properties of nitric oxide.