Neuropeptides may influence the recruitment, proliferation, and activation of leukocytes. On the other hand, inflammatory cells may modulate the neuronal phenotype and function. The functional relevance of the excitatory NANC nervous system and its interaction with the immune system in asthma still remains to be elucidated.
Abstract The human airways are innervated via efferent and afferent autonomic nerves, which regulate many aspects of airway function.
The major function of the lungs is to perform gas exchange, which requires blood from the pulmonary circulation. This blood supply contains deoxygenated blood and travels to the lungs where erythrocytes, also known as red blood cells, pick up oxygen to be transported to tissues throughout the body. The pulmonary artery is an artery that arises from the pulmonary trunk and carries deoxygenated, arterial blood to the alveoli. The pulmonary artery branches multiple times as it follows the bronchi, and each branch becomes progressively smaller in diameter.
One arteriole and an accompanying venule supply and drain one pulmonary lobule. As they near the alveoli, the pulmonary arteries become the pulmonary capillary network. The pulmonary capillary network consists of tiny vessels with very thin walls that lack smooth muscle fibers. The capillaries branch and follow the bronchioles and structure of the alveoli. It is at this point that the capillary wall meets the alveolar wall, creating the respiratory membrane. Once the blood is oxygenated, it drains from the alveoli by way of multiple pulmonary veins, which exit the lungs through the hilum.
Dilation and constriction of the airway are achieved through nervous control by the parasympathetic and sympathetic nervous systems. The parasympathetic system causes bronchoconstriction , whereas the sympathetic nervous system stimulates bronchodilation.
Reflexes such as coughing, and the ability of the lungs to regulate oxygen and carbon dioxide levels, also result from this autonomic nervous system control.
Sensory nerve fibers arise from the vagus nerve, and from the second to fifth thoracic ganglia. The pulmonary plexus is a region on the lung root formed by the entrance of the nerves at the hilum. The nerves then follow the bronchi in the lungs and branch to innervate muscle fibers, glands, and blood vessels. Each lung is enclosed within a cavity that is surrounded by the pleura. The right and left pleurae, which enclose the right and left lungs, respectively, are separated by the mediastinum.
The pleurae consist of two layers. The visceral pleura is the layer that is superficial to the lungs, and extends into and lines the lung fissures Figure. In contrast, the parietal pleura is the outer layer that connects to the thoracic wall, the mediastinum, and the diaphragm.
The visceral and parietal pleurae connect to each other at the hilum. The pleural cavity is the space between the visceral and parietal layers. Respiratory System. You need flash to view this Click here to download the latest flash plugin. Bronchioles have a much smaller diameter than the bronchi about 0. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia.
All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation.
This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the paper and its Supporting Information files.
Competing interests: The authors have declared that no competing interests exist. In humans, airway smooth muscle ASM tone is largely determined by parasympathetic cholinergic control, which is operated by the vagus that innervates the large airways [ 1 ].
The central autonomic control of the ASMs tone is a complex and interconnected system with multiple parallel pathways that contribute to regulate the parasympathetic cholinergic outflow in multiple organs and systems.
Dysfunction or dysregulation of the autonomic control of ASMs contributes to the pathogenesis of asthma and chronic obstructive pulmonary disease, and may also produce the respiratory symptoms associated with cardiovascular diseases [ 2 — 5 ]. A comprehensive knowledge of the mechanisms regulating ASMs tone would be crucial for a better understanding and treatment of obstructive pulmonary diseases.
However, there are still tremendous gaps in our understanding of airway neural control, even in the healthy lung. One of these gaps is related to the central control of autonomic tone and to the integration of different afferent inputs. Due to the limited availability of methods capable of simultaneously assessing ASMs tone and cardiovascular regulation, the interaction between these two systems remains poorly studied.
In particular, it is not known whether parasympathetic activation acts on the bronchial tone and cardiovascular system in parallel, or, alternatively, whether the regulation of the two systems is more determined by local factors acting on each system independently. Moreover it is unclear whether all stimuli associated with parasympathetic activation have similar effects or whether different stimuli might have different effects according to their specific nature.
We hypothesized that interventions that stimulate the cardiovascular and respiratory systems through parasympathetic activation would cause both cardiovascular depression and airway narrowing, while interventions associated with a selective direct stimulation of either system would produce independent responses. To this aim we evaluated the simultaneous effects of different kinds of stimulations, all associated to parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation to test whether the control of the cardiovascular and respiratory systems acts separately or in parallel, according to their different needs.
In particular we evaluated the effect of neck suction, oxygen inhalation, slow breathing common in Yoga and other similar practices and methacoline Mch administration in a group of healthy volunteers. Neck suction is a pure carotid baroreceptors stimulation [ 6 — 9 ]. Oxygen inhalation increases cardiac parasympathetic activity [ 10 — 12 ], but may also alter gas exchange and consequently affect ventilation.
Slow breathing increases the vagal arm of the cardiac baroreflex [ 13 — 16 ], but also modifies gas exchange [ 17 , 18 ] and, through the increase in tidal volume, may also affect bronchial tone [ 19 ].
Finally, inhaled MCh induces airway narrowing as a result of parasympathetic activation, but may also activate sympathetic reflexes in other systems due to the associated hypoxemia [ 20 ].
The study was conducted in 13 healthy subjects whose characteristics are reported in Table 1. None of them was taking any treatment at the time of the study. The study was approved by the Ethical Committee of the S. Detailed description of methodology and data analysis is reported in S1 Supporting Information.
Electrocardiogram was measured by placing three electrodes on the patient's anterior chest wall. Oxygen saturation SaO 2 was measured at the finger with a pulse oxymeter and expired carbon dioxide CO 2 by a capnograph. Oxygenation perfusion at the tissue level was estimated at the left forearm by a Near Infrared Spectroscope. Values are expressed as tissue oxygen saturation index TO 2 I. Continuous noninvasive arterial blood pressure was monitored via cuffs positioned on the middle finger of the right arm held at the heart level.
All signals were simultaneously acquired at Hz on a Macintosh laptop Apple, Coupertino, CA with a 12 channel acquisition system. Airway mechanics was measured by multiple frequency forced oscillation technique FOT at 5, 11, and 19 Hz [ 21 — 23 ]. Respiratory system resistance was computed by a least squares algorithm [ 24 , 25 ] at 5 Hz R 5 and 19 Hz R Oxygen O 2 inhalation was obtained by breathing supplemental O 2 for 11 min.
Measurements were taken during the last 5 min. Baroreceptors stimulation was obtained by sinusoidal suction applied to a lead collar positioned around the neck by a vacuum system via a computer-controlled valve which produced a controlled suction loss [ 26 ]. Measurements were taken during 2 min of sinusoidal suction from 0 to mmHg at 0. Two min after the end of the inhalation, measurements were taken during 2 min of spontaneous breathing. The study was conducted in the sitting position. All measurements described above were performed at baseline conditions for 4 min, and then in random order during O 2 breathing, slow deep breathing, and neck suction at 0.
The bronchial challenge was always performed at the end of study to avoid the long-lasting effects of the constrictor agent on airway tone control. The latter was the mean value computed from seven different tests [ 27 , 28 ]. Average heart rate HR was calculated for each sequence.
The parasympathetic effects of neck suction were estimated from the power spectra of the RR interval and blood pressure signals evaluated at 0. R 5 and R 19 , evaluated during tidal inspiration, were taken as indexes of total and central airways size, respectively [ 21 ]. This allowed separating the effects of the parasympathetic stimuli from depth of breathing on bronchomotor tone.
Tidal volume and resistance at 5 R 5 and 19 Hz R 19 are shown as a function of time in the upper, mid, and lower panels, respectively.
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