Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position

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.

Regional lung ventilation in humans during hypergravity studied with quantitative SPECT

“…In prone posture, on the other hand, no change in blood flow distribution was seen after NO synthase inhibition. 51 Later, in a study by Sánchez-Crespo et al, 53 NO produced in the upper airways was also confirmed to have a significant influence on the distribution of lung blood flow.…”

Breath Tools: A Synthesis of Evidence-Based Breathing Strategies to Enhance Human Running

“…It is functionally equipped to humidify, warm, and filter inspired air ( Walker et al, 2016 ). It also increases nitric oxide production in the airway, and has positive effects upon pulmonary perfusion ( Sanchez Crespo et al, 2010 ), head posture ( Sabatucci et al, 2015 ), and cognitive function ( Zelano et al, 2016 ). Mouth breathing is more common during exercise and for those with nasal breathing difficulties ( Niinimaa, 1983 ).…”

“…With an adaptation period, nasal breathing during exercise may cause reduced BR, reduced hypocapnia, and increased nitric oxide production ( Dallam et al, 2018 ). Nitric oxide production is itself beneficial as a vasodilator and bronchodilator ( Sanchez Crespo et al, 2010 ; Thornadtsson et al, 2017 ), perhaps reducing the risk for flow limitation. While nasal breathing utilizes a smaller airway, which is a limitation at higher exercise intensities, it appears to increase diaphragmatic function ( Trevisan et al, 2015 ), which could be a long-term advantage (see section “Deep”).…”

Distinguishing science from pseudoscience in commercial respiratory interventions: an evidence-based guide for health and exercise professionals

“…Articles were excluded if they reported on exogenous (supplementary) NO inhalation, if they studied exhaled NO as a tool for assessing airway inflammation, or if nasal breathing was studied in combination with other breathing interventions (e.g., deep/slow breathing). Using single photon emission computed tomography during separate bouts of upright nasal or oral breathing in healthy adults, Crespo et al (2010) found that nasal breathing elicited blood flow redistribution from caudal and dorsal regions of the lung to the less-perfused cranial and ventral regions. For the poorly perfused lung regions, such as the apical region, this represented a 24% increase in blood flow.…”

“…Others suggest that nasal breathing might attenuate pulmonary hypertension by vasodilating the pulmonary vasculature (Settergren et al 1998). Although exogenous (supplementary) NO is known to reduce vascular resistance and increase pulmonary blood flow in healthy and patient populations (Settergren et al 1998;Crespo et al 2010), the concentration of endogenous (nasally-derived) NO is considerably lower than the concentrations used in NO-enriched air (Törnberg et al 2002). Therefore, an important consideration is whether increased NO uptake via nasal breathing exerts meaningful effects in healthy or patient populations.…”