Regulation of ciliary beat frequency by autonomic mechanisms: in vitro

1988 ◽  
Vol 65 (4) ◽  
pp. 1895-1901 ◽  
Author(s):  
L. B. Wong ◽  
I. F. Miller ◽  
D. B. Yeates

The ciliated epithelium of the mammalian trachea separates the neurohumoral milieu of the tissue from that of the environment of the airway lumen. To determine whether specific autonomic receptors regulating ciliary beat frequency (CBF) were located on mucosal or serosal sides, we measured CBF by heterodyne mode correlation analysis laser light scattering in bovine tracheal tissues mounted in a two-sided chamber. A beta 2-adrenergic agonist, fenoterol, at 10(-7) M, stimulated serosal CBF from 7.9 +/- 1.3 to 20.2 +/- 5.8 Hz (P less than 0.01) and mucosal CBF from 6.6 +/- 0.9 to 14.7 +/- 4.6 Hz (P less than 0.01). A muscarinic cholinergic agonist, methacholine, at 10(-7) M, increased mucosal CBF from 8.4 +/- 1.0 to 19.5 +/- 5.5 Hz (P less than 0.01) and serosal CBF from 8.0 +/- 0.9 to 15.4 +/- 5.0 Hz (P less than 0.01). The differences in stimulation of CBF on the mucosal and serosal sides between fenoterol and methacholine were significant (P less than 0.01). Studies in which these autonomic agonist stimulating effects were inhibited by their respective antagonists, propranolol and atropine sulfate, demonstrated that CBF can be regulated independently by mediators both in the submucosa and within the mucus lining.

1990 ◽  
Vol 68 (6) ◽  
pp. 2574-2580 ◽  
Author(s):  
L. B. Wong ◽  
I. F. Miller ◽  
D. B. Yeates

To determine the possible involvement of neural and cyclooxygenase pathways whereby irritants might affect cilia activity in vivo, the temporal response of canine tracheal ciliary beat frequency (CBF) to the inhaled surrogate irritant capsaicin was studied. CBF was measured on the ventral midtracheal surface of barbiturate-anesthetized eucapnically ventilated beagle dogs by heterodyne-mode laser light scattering. After base-line CBF was established, hexamethonium bromide (2 mg/kg iv), ipratropium bromide (0.5 microgram/kg iv), indomethacin (2 mg/kg iv), or intravenous 0.9% saline was administered. Aerosolized 3 Z 10(-9) M capsaicin in 0.9% saline was delivered for 2 min, and CBF was measured for the following 60 min. Control experiments used 0.9% saline sham aerosol with a 0.9% saline sham block. Aerosolized capsaicin stimulated CBF from a base line of 6.2 +/- 1.4 (SD) Hz (n = 230) to a mean maximum of 17.7 +/- 7.3 Hz (n = 16) 23 min after aerosol delivery, and CBF returned to base line within 60 min. Neither hexamethonium bromide, ipratropium bromide, nor indomethacin changed CBF from base-line values. The episodic CBF stimulatory response to capsaicin after commencement of aerosol was completely inhibited by hexamethonium bromide. Ipratropium bromide partially inhibited the first 15 min and totally inhibited the following 45 min of stimulatory response. Indomethacin inhibited the initial 15 min but had less effect on the following 45 min of stimulatory response. These data indicate that multiple stimulatory mechanisms function over a prolonged period of time to affect the removal of irritants from the airways and that these mechanisms differ from those involved in the maintenance of basal CBF.


1988 ◽  
Vol 65 (2) ◽  
pp. 971-981 ◽  
Author(s):  
L. B. Wong ◽  
I. F. Miller ◽  
D. B. Yeates

beta 2-Adrenergic bronchodilator and muscarinic cholinergic bronchoconstrictor agonists both stimulate ciliary activity in vitro. To test the hypothesis that increases in autonomic activity would result in increases in ciliary beat frequency (CBF) in vivo, a correlation analysis heterodyne laser light-scattering system was developed and validated to measure the stimulating effects of sympathomimetic and parasympathomimetic agonists on tracheal CBF in intact, anesthetized beagles. The mean baseline CBF from 42 studies of 274 measurements in 9 (5 male and 4 female) adult beagles was 6.6 +/- 1.1 Hz. The stimulating effects of a beta 2-adrenergic agonist, fenoterol, and a muscarinic cholinergic agonist, methacholine, on CBF were studied on four and eight beagles, respectively. The studies were randomized and blinded. Aerosolized 10(-5) M fenoterol stimulated the CBF from the base line of 6.8 +/- 2.5 to 32.0 +/- 17.9 Hz in four dogs. Aerosolized methacholine stimulated the CBF from the base line of 5.8 +/- 0.7 to 9.4 +/- 3.0 Hz for 10(-8) M, and to 12.6 +/- 3.1 Hz for 10(-6) M in eight dogs. These are the first data obtained in intact animals that demonstrate CBF in the lower respiratory tract is regulated by autonomic agonists.


1994 ◽  
Vol 77 (3) ◽  
pp. 1239-1245 ◽  
Author(s):  
M. Eljamal ◽  
L. B. Wong ◽  
D. B. Yeates

We questioned whether the prolonged stimulation of ciliary beat frequency (CBF) to a short exposure of low-dose capsaicin (Wong et al. J. Appl. Physiol. 68: 257–2580, 1990) could be due to the activation of indirect pathways involving neural reflexes initiated independently in the bronchi and alveoli. Tracheal CBF (CBFtr) was measured temporally in anesthetized groups of 10 dogs by means of heterodyne-mode correlation analysis laser light scattering. To elucidate the site of the afferent neural stimulation and the efferent mediators affecting the ciliated epithelium, capsaicin (3 nM) aerosol was delivered for 4 min, either predominantly to the bronchi or to the alveolar regions, with use of pulsed aerosol techniques. This resulted in 13 pg of bronchial (85%) and 10 pg of alveolar (96%) capsaicin deposited, which caused marked stimulation of CBFtr with maxima at 7 and 35 min, respectively. Prior administration of aerosolized indomethacin to the bronchi or aerosolized cromolyn to the alveoli inhibited the bronchial and alveolar responses, respectively. Prior administration of aerosolized hexamethonium to the tracheal lumen blocked the stimulatory CBFtr responses from both capsaicin challenges. Ipratropium or propranolol aerosols delivered to the tracheal lumen also inhibited these responses. It is proposed that these pathways comprise one set of sensitive mechanisms to ensure a prolonged stimulation of CBF to effect the removal of secretions and the irritant from the lungs.


1995 ◽  
Vol 20 (5) ◽  
pp. 465-469 ◽  
Author(s):  
A. M. AGIUS ◽  
M. WAKE ◽  
A. L. PAHOR ◽  
A. SMALLMAN

1988 ◽  
Vol 65 (4) ◽  
pp. 1617-1620 ◽  
Author(s):  
D. R. Maurer ◽  
J. Liebman

Consumption of ethanol can impair lung function and slow total lung clearance. High concentrations of ethanol have been shown to slow or arrest ciliary beating. This study examined the effects of concentrations of alcohol comparable to blood levels achieved from social drinking on ciliary beat frequency. We obtained ciliated cells by brushing the trachea of unanesthetized sheep during fiber-optic bronchoscopy. The cells were suspended in a perfusion chamber and physiological conditions were maintained in vitro. Ciliary beat frequency and synchrony were determined by slow-motion analysis of video images obtained by interference contrast microscopy. Metachronal ciliary coordination was observed in all preparations. The ciliary beat frequency was stimulated at ethanol concentrations from 0.01 up to but not including 0.1%, unchanged at 0.5 and 1%, and slowed at 2%. While confirming inhibition of ciliary motility at very high ethanol levels, we observed no acute impairment of ciliary function at ethanol concentrations comparable to those achieved from social drinking. Indeed, we found an unexpected stimulation of ciliary beating at low levels of ethanol. How this alteration in ciliary beating would affect pulmonary clearance remains unknown at this time.


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