Nasal Nitric Oxide: Nature’s Answer to Gravity?

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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.