Nitric Oxide Might Outweigh All Other Benefits of Nose Breathing

Key Points

• Nasal nitric oxide (NO) acts as our body’s first line of defense against airborne pathogens

• Nasal NO reduces blood pressure, redistributes blood flow, and increases gas exchange

• The humidifying effects of the nose might not be as important as NO

The Breathing Diabetic Summary

Nitric oxide (NO) has, somewhat quietly, become a staple of breathing science.  NO is produced in the nasal airways and carried into the lungs with each (nasal) breath we take.  This review discussed nasal NO, its origins, and its physiological effects in the body.

The general consensus is that NO is produced in the paranasal sinuses and is continuously released into the nasal airways.  Because of this continuous release, NO’s concentration is dependent on flow rate.  A lower flow rate will allow more NO to build up, thus bringing higher concentrations down into the lungs with each breath.   

This could be yet another benefit of slow breathing: Slower flow rates will increase NO. Each breath then brings in a higher concentration of NO, redistributing blood flow, increasing gas exchange, and potentially increasing infection-fighting capabilities.

Which brings us to the next physiological effect of nasal NO: Host defense.  Some bacteria die when NO concentrations are as low as 100 parts per billion (ppb).  In the paranasal sinuses, the concentration can be as great as 30,000 ppb(!).  Thus, nasal NO might be the first line of defense against airborne bacteria, acting to sterilize the incoming air and reduce infection. 

Nasal NO also increases arterial oxygenation and reduces blood pressure in the lungs.  For example, one study showed that nasal breathing increased tissue oxygenation by 10% when compared to mouth breathing.  That’s pretty remarkable.

For example, one study showed that nasal breathing increased tissue oxygenation by 10% when compared to mouth breathing.

Another study showed that when mouth breathers were given supplemental NO, arterial oxygenation increased and and lung blood pressure decreased similar to nose breathing.  Interestingly, if the mouth breathers were just given moistened air (without NO), these effects did not occur.  Thus, the main benefits of nasal breathing might be due to NO, not the warming and humidifying effects that are typically touted (although they clearly help).

Finally, widening the nostrils via nasal tape also increases arterial oxygenation during breathing at rest.  This could partially be due to an increased delivery of NO to the lungs.  We can naturally unblock our noses using simple breath hold techniques or use something like Intake Breathing for assistance.

Overall, this study highlighted several important aspects of nasal NO.  It acts as our body’s first line of defense against airborne pathogens by sterilizing incoming air.  Then, as NO travels into the lungs, it reduces blood pressure, redistributes blood flow, and increases gas exchange, leading to greater arterial oxygenation.  Finally, we learned that the humidifying effects of the nose might not be as important as NO. 

I am continually amazed by the many roles of nitric oxide in the body.  I believe it might be the most important aspect of nasal breathing. 

Journal Reference:

Lundberg JO, Weitzberg E.  Nasal nitric oxide in man.  Thorax.  1999;54(10):947-52.

Nasal Nitric Oxide: Nature’s Answer to Gravity?

Key Points

• Nitric oxide redistributes blood flow in the lungs to be more uniform

• Nitric oxide increases gas exchange in the lungs

• Nasal nitric oxide might be an evolutionary adaptation to counter gravity

The Breathing Diabetic Summary

Blood flow in the lungs is essential for gas exchange and defense against infections. However, lung blood flow is not as uniform as we might think. And, although several factors account for this, gravity plays a significant role.  Gravity acts to focus blood flow toward the bottom of the lungs.  

Interestingly, in humans and higher primates, a large amount of nitric oxide (NO) is released in the nasal passages. As we learned, NO is critical for blood flow and whole-body oxygenation. The authors of this study wondered if nasal NO might also redistribute blood flow in the lungs, thus countering the effects of gravity and increasing gas exchange in the lungs. This adaptation would have allowed us to evolve into the bipedal mammals we are today.

To test this, they examined how different breathing protocols affected lung blood flow. Participants were injected with a radionuclide that acted as a passive tracer of blood flow, which could then be imaged to show relative “heat maps” of blood flow in the lungs.

Fourteen participants were broken into three groups. The first group served as a control to ensure the radiotracer imaging technique worked as intended. The second group was used to see how nasally produced NO affected lung blood flow. These participants sat in an upright position and breathed through their mouths for 20 min. The tracer was injected, and their lung blood flow was imaged. Then, they switched to nasal breathing for 10 min. Tracer was again injected imagery was taken.

The final group was used to see if NO was, in fact, the driver of lung blood flow redistribution. These participants breathed through their mouths but were given supplemental NO. If NO was the driver, mouth breathing with additional NO should result in similar blood flow redistribution as nasal breathing.

They found that nasal breathing redistributed blood flow both vertically and horizontally in the lungs, making it more uniform. The same occurred when mouth breathing with supplemental NO. Thus, NO, whether produced naturally in the nasal passages or supplemented, acts to redistribute blood flow and increase gas exchange in the lungs.

The authors hypothesize that the NO produced in the nasal passages is an evolutionary adaptation to walking upright.  The NO acts to make blood flow and gas exchange more uniform, thus countering the effects of gravity.

In summary, nasal nitric oxide counteracts the effects of gravity and makes lung blood flow more uniform in the upright position. Interestingly, this only occurs in humans and higher primates. Thus, NO production in the upper airways might have been a critical evolutionary adaptation that allowed us to walk upright.

Abstract

There are a number of evidences suggesting that lung perfusion distribution is under active regulation and determined by several factors in addition to gravity. In this work, we hypothesised that autoinhalation of nitric oxide (NO), produced in the human nasal airways, may be one important factor regulating human lung perfusion distribution in the upright position. In 15 healthy volunteers, we used single-photon emission computed tomography technique and two tracers (99mTc and 113mIn) labeled with human macroaggregated albumin to assess pulmonary blood flow distribution. In the sitting upright position, subjects first breathed NO free air through the mouth followed by the administration of the first tracer. Subjects then switched to either nasal breathing or oral breathing with the addition of exogenous NO-enriched air followed by the administration of the second tracer. Compared with oral breathing, nasal breathing induced a blood flow redistribution of approximately 4% of the total perfusion in the caudal to cranial and dorsal to ventral directions. For low perfused lung regions like the apical region, this represents a net increase of 24% in blood flow. Similar effects were obtained with the addition of exogenous NO during oral breathing, indicating that NO and not the breathing condition was responsible for the blood flow redistribution. In conclusion, these results provide evidence that autoinhalation of endogenous NO from the nasal airways may ameliorate the influence of gravity on pulmonary blood flow distribution in the upright position. The presence of nasal NO only in humans and higher primates suggest that it may be an important part of the adaptation to bipedalism.

Journal Reference:

Sánchez Crespo A, Hallberg J, Lundberg JO, Lindahl SG, Jacobsson H, Weitzberg E, Nyrén S.  Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position.  J Appl Physiol.  2010;108:181–188.

The protective role of nitric oxide during adaptation to hypoxia

Key Points

• Adaptation to hypoxia increases NO production and storage

• Simultaneously, adaptation to hypoxia protects against NO over- and under-production

Breathing Blueprint Summary

A paper we recently reviewed found that the production and storage of nitric oxide (NO) increases significantly during adaptation to hypoxia.  This paper wanted to see what would happen during adaptation to hypoxia in disorders of either NO over-production or NO deficiency.

Three different types of Wistar rats were studied.  The first was a model of NO overproduction (NO+), the second a model of NO deficiency (NO-), and the third a control group.

The same protocol from their previous work was used for adaptation to hypoxia: They gradually adapted mice to hypoxia in an altitude chamber simulating ~5000 m (hypobaric hypoxia).  The mice completed 40 sessions.  They started at 10 min the first session, then 20 min the second session, and so on until they reached 5 hours of simulated altitude per session.

After the full acclimation, the control mice nearly doubled their NO metabolites.  Their NO storage had significantly increased as well.  These results indicated that NO production and storage increased due to adaptation to hypoxia.

These adaptations were beneficial for the other mice studied.  The NO+ mice that were not acclimated to hypoxia showed a drop in blood pressure of about 36 mm Hg.  The NO+ mice that were acclimated to hypoxia only showed a 19 mm Hg drop.

Similarly, adaptation to hypoxia protected the NO- mice as well.  Without hypoxia, their blood pressure increased ~80 mm Hg.  With adaptation, it only increased ~20 mm Hg.

These results indicate that adaptation to hypoxia protects against both over- and under-production of NO.

The body ramps up production of NO while simultaneously increasing NO storage to an even greater extent.  This prevents severe drops in blood pressure, but also ensures that NO is available “if needed.”

The final sentence from the abstract sums it up nicely:

“The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency.”

Abstract

Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency.

Journal Reference:

Manukhina EB, Mashina SY, Smirin BV, et al. Role of nitric oxide in adaptation to hypoxia and adaptive defense. Physiol Res. 2000;49(1):89-97.