Nitric oxide signaling in health and disease – The Mahathian Post

In a recent review article in cellResearchers Jon Lundberg and Eddie Weitzberg from the Department of Physiology and Pharmacology at the Karolinska Institute summarize the research on nitric oxide (NO) while focusing on what is happening right now.

When NO was discovered as a neurotransmitter almost 40 years ago, it came as a surprise to the entire research world. Hardly anyone would have thought that a gas that is best known as a harmful air pollutant is created in our body and performs a number of very important functions. Among other things, regulation of blood flow and control of blood pressure, which was also awarded the Nobel Prize in 1998.

According to the authors, although the field is very large with more than one hundred thousand publications on this topic, surprisingly few new clinical methods or new treatments have emerged from it. But two methods stand out from a Swedish perspective, they write:

“Nevertheless, in this context, it is fun that two out of five NO-related methods approved by the Food and Drug Administration (FDA) are based on original discoveries from the Karolinska Institutet. It is the method of administering inhaled NO to newborns with severe lung disease and the method of measuring exhaled NO as a marker of inflammation in asthma,” says Jon Lundberg, professor of nitric oxide pharmacology.

Other, newer methods come from the pharmaceutical company These include the so-called guanylyl cyclase stimulators, which are drugs that act downstream of NO to increase the formation of cGMP, cyclic guanosine monophosphate, a cyclic nucleotide that acts as a messenger in cells. Today, these drugs are used, among other things, e.g heart defect and so-called pulmonary hypertension. Other NO-related drugs include the vasodilator nitroglycerin, which is used for angina and works through NO release. The article also mentions sildenafil, a drug used to treat impotence that inhibits the breakdown of cGMP.

Proven effect on physical performance

The authors of the review article also shed light on the alternative route to NO formation that they discovered in the 1990s, namely via so-called inorganic nitrate. It is found in large amounts in certain vegetables and is converted into NO in our body by a system that also involves the bacteria in the oral cavity. The usual path of NO formation in the body runs via so-called NO synthases, which form NO from L-arginine and oxygen. NO from nitrate is independent of NO synthase and does not require oxygen, but it is still the same NO and has the same effects on the body. In this way, nitrate intake can lower blood pressure, among other things. Nitrate has another effect that Lundberg and Weitzberg accidentally discovered; it reduces oxygen consumption during physical work, so the same work can be done with less oxygen consumption. The effect is used today by athletes all over the world to increase performance:

“We are actually a little proud that the International Olympic Committee (IOC) recently published a consensus report stating that nitrate is one of only four dietary supplements which have been shown to impact physical performance,” concludes Jon Lundberg.