The Biggest Nitric Oxide Reservoir in the Body?

Join Dr. Van Dyken as she discusses the biggest nitric oxide reservoir in the body, the skeletal muscle!

Timestamps:
00:00 Intro, review of basic NO physiology
02:36 Dietary Nitrates as a way to raise NO in muscle
03:44 Functions of Nitric Oxide in Muscle, SNO-hemoglobin
06:26 Synthesis of NO in the muscle
08:18 Wrap-up

References:
1. Nitric Oxide as a determinant of longevity and healthspan. https://www.mdpi.com/1422-0067/24/19/14533#:~:text=The%20master%20molecular%20regulators%20and,radical%20to%20promote%20healthy%20aging
2. Dietary Nitrate and Nitric Oxide Metabolism. https://pubmed.ncbi.nlm.nih.gov/32735111/
3. The role of hemoglobin in nitric oxide transport in vascular system.
https://www.sciencedirect.com/science/article/pii/S2590093520300084
4. Effect of dietary nitrates on oxygen cost during exercise. https://pubmed.ncbi.nlm.nih.gov/17635415/
5. Supplementation with NO precursurs for strength performance https://pubmed.ncbi.nlm.nih.gov/36771366/
6. Physiology of NO in skeletal muscle. https://journals.physiology.org/doi/full/10.1152/physrev.2001.81.1.209
7. Skeletal Muscle as an endogenous NO reservoir. https://pubmed.ncbi.nlm.nih.gov/25727730/
8. Skeletal Muscle Nitric Oxide signaling and exercise. https://journals.physiology.org/doi/full/10.1152/ajpendo.00667.2011?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org

Aloha I’m your Menan dyin MD from out of the doldrums on this channel we talk a lot about nitric oxide we go into the nitty-gritty today we’re going to explore yet one additional facet of the nitric oxide story we will be discussing the biggest nitric oxide Reservoir in

The human body skeletal muscle I know it sounds a little strange because we usually think of nitric oxide in the blood and the blood vessels and its increasing blood supply to the body that way because of this I was a little skeptical when I first heard about

Muscle being such a huge nitric oxide Reservoir but the data behind this is sound and we can use this knowledge to our advantage but I’m getting ahead of myself let’s start with A Brief Review of the basics nitric oxide often abbreviated as n o is a small molecule with a

Significant impact on our health it’s a cellular signaling molecule that plays a pivotal role in various physiological processes one recent paper even went so far as to call nitric oxide quote a master molecular regulator determining longevity and health span end quote along those lines we do know that continuous nitric oxide generation is

Essential for the maintenance of cellular function and our overall health and we also know that older age and several chronic disease conditions are characterized by lower levels of nitri oxide one of Nitric oxide’s most well-known functions is as a vasod dilator this means it has the ability to

Relax and expand our blood vessels ensuring that oxygen and essential nutrients are efficiently delivered to tissues especially during periods of increased demand like exercise nitric oxide is a molecule that has a very short half-life on the order of seconds once it’s produced it’s used up really quickly or it gets met metabolized into

Other forms so it’s commonly converted back into nitrate and nitrite if it’s not needed so what does the body do with all this excess nitrate and nitrate well it forms a reservoir it stays it for a rainy day for a day when we really need nitric oxide so this nitrate and nitrate

Can be stored in our body and rapidly converted to nitric oxide when our body demands it I like to think of nitrate and nitrate as ready mix ingredients for nitric oxide it doesn’t take much to convert it to nitric oxide right at the very instant our body requires it for

Its essential functions backing up even more let’s take a look at the really big picture we can get nitrates from our diet great sources of dietary nitrates are beetroot arugula or rocket kale lettuce and spinach these nitrates get converted to nitrites NO2 and then back again to nitrates NO3 these nitrates and

Nitrites get transported from from our GI tract into the blood where they’ve got options they can hang out there and get converted to nitric oxide or they can go into the skeletal muscle where they also can be converted to nitric oxide I used to think that nitrate was

Mainly stored in the blood that blood was the reservoir but Recent research tells us otherwise it turns out that the nitrate concentration in skeletal muscle is much higher than that in blood adding to this muscle nitrate stores are EX exquisitly sensitive to high dietary nitrate supplementation and

Deprivation this means we can build up our muscle nitrate reservoirs quite quickly we can get from deficient to full in only 3 days we’re learning that nitric oxide has many different functions in the tissues besides just vasod dilation along those lines besides being stored as nitrate and nitrite

Nitric oxide can be stored on the hemoglobin molecule of the blood in doing so nitric oxide gains an additional function it actually controls blood flow to certain tissues this does get a little sciency so put your science hats on and stick with me for just one

Moment and it’ll all make sense our red blood cells have hemoglobin molecules on them no can bind to the hemoglobin to form a molecule called s nitroso hemoglobin or snow hemoglobin for short this snow hemoglobin molecule is the bioactive form of nitric oxide that controls blood flow to the

Tissues when oxygen and snow hemoglobin laiden red blood cells reach the microvascular arteriales and capillaries of the tissues like the muscle hemoglobin senses how much oxygen is present if the oxygen level in the tissue is low the hemoglobin will release both oxygen and snow hemoglobin the oxygen nourishes surrounding tissues

And the snow hemoglobin signals for the blood vessels to widen which results in an even greater blood flow and oxygen delivery to the tissues it’s a genius system in contrast when oxygen levels are high hemoglobin does not release oxygen or snow hemoglobin there’s no need to release all that if the tissues

Are well oxygenated our body will save that resource for another time and another area so if you look at the big picture the system makes sense when you consider that the body has to regulate blood flow at the level of individual tissues and micro capillaries we only

Have so much blood in our body like 6 liters and our body has to prioritize where it goes an exercising muscle needs more blood delivered to it compared to a resting muscle many have theorized that having enough of that muscle reservoir of nitric oxide will improve athletic performance somewhere between 40 to 90%

Of athletes use dietary supplements to be honest though the studies looking at nitrate intake in athletic performance they’re all over the place some show Improvement in in performance others show no improvement a landmark study by Larsson at all discovered that sodium nitrate supplementation reduced the oxygen cost of submaximal cycling

Another study showed similar results with beetroot juice these results suggest that dietary nitrate permits more muscular work to be performed per unit time for the same energy cost so basically the efficiency of skeletal muscle contraction is enhanced now when we think of no production we often consider synthesis in the endothelial

Cells lining our blood vessels however our skeletal muscle plays a crucial role in this narrative too within these muscles an enzyme called neuronal nitric oxide synthes or ennos for short is a primary producer of no this localized production of no in the muscles has several implications from modulating

Glucose uptake which is vital for energy to potentially influencing muscle repair and growth but the story doesn’t end there within muscle tissue there’s a protein called myoglobin which primarily functions to store and deliver oxygen when myoglobin interacts with no a compound called s nitroso myoglobin or snow myoglobin is formed this compound

Is particularly intriguing because it acts as a reservoir for no o storing it and releasing it under specific conditions such as during muscle contraction or in low oxygen environments now let’s introduce prod another dimension to this narrative nitrate our skeletal muscles have the capability to store nitrate a compound

That can be a precursor for no production through a series of biochemical reactions like we talked about nitrate can be reduced first to nitrite and subsequently Eno this provides an alternative and an efficient route for Eno production in muscles especially in conditions where oxygen can be limited the implications of this

Nitrate nitrite noo pathway are vast Beyond just muscle function and Metabolism there’s evidence to suggest that this pathway might have protective effects on the heart especially against conditions like esea reperfusion injury this is a scenario where tissue deprived of oxygen due to reduced blood flow experiences damage when blood flow is

Restored in wrapping up it’s clear that our muscles are not just about strength and movement they are biochemically active they’re their own organ they’re playing roles in the storage production of molecules that have wide reaching effects on our health from the production of no via enzymes like Enos

To the storage of nitrate and its potential conversion to no our muscles are Central players in a complex physiological dance as far as I’m concerned more muscle equals more nitric oxide storage capacity if you like this video please give it a thumbs up if you want to show us some real support

Subscribe and let me know in the comments below what you are doing to increase your muscle mass and your nitric oxide levels until next time cherish your health and aloha