Blood sinuses in the submucosa of the large airways of the sheep.

We have studied the airway vasculature in sheep using light and transmission electron microscopy, as well as arterial and venous (retrograde) injections of anatomical corrosion compound and latex. Vascular casts were viewed by scanning electron microscopy. There is a complex network of blood sinuses of large diameter (up to 500 microns) in the submucosa of the large airways.

Airway mucus.

Airway surface liquid (ASL), a mixture of periciliary fluid and submucosal gland secretions, was collected from the ferret isolated trachea in vitro. The trachea was closed, without possibility of evaporation. The collected ASL was hyperosmolar (310-350 mosmol.

The transport of albumin across the ferret in vitro whole trachea.

1. The whole trachea of the ferret has been isolated in vitro in an organ bath and used to study the transport of bovine serum albumin (BSA) and two dextrans (70,000 and 9000 Da) from external buffer solution to air-filled lumen, assessed by fluorescent-labelled tracers. 2.

Effects of neuropeptides and capsaicin on the canine tracheal vasculature in vivo.

1. The nonadrenergic, noncholinergic nervous system may control the airway vasculature via various neuropeptides. We have perfused the cranial tracheal arteries of the anaesthetized dog and investigated the effects of neuropeptides and capsaicin (which is supposed to release neuropeptides from sensory nerve endings) on the tracheal vasculature by injecting them locally into the perfusion system.

The effects of a mixture of surface-active agents (Sonarex) on upper airways resistance and snoring in anaesthetized dogs.

We measured upper airways resistance from the trachea and from the pharynx to the atmosphere, EMG of the genioglossus muscle and the sound of snoring, in anaesthetized greyhounds, breathing spontaneously through the upper airways. Using extra-corporeally produced continuous flow we determined flow/pressure curves for the upper airways and resistances from the trachea and from the pharynx. We tested the effects of 0.

Upper airways resistance and snoring in anaesthetized dogs.

We have measured upper airways resistance from the trachea and from the pharynx to the atmosphere, EMG of genioglossus muscle, and the sound of snoring, in anaesthetized greyhounds breathing spontaneously through the upper airways. Using extra-corporeally produced continuous flow we determined flow/pressure curves for the upper airways in an expiratory direction and analysed them in terms of resistances from the trachea and from the pharynx. Resistances and other variables were determined with the nose open and the nostrils blocked.

H1- and H2-receptor characterization in the tracheal circulation of sheep.

1. The effects of histamine, the specific H1-agonist SKF 71481-A2 and the H2-agonist dimaprit were examined on tracheal vascular resistance in sheep anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures.

Chloride transport in apical membrane vesicles from bovine tracheal epithelium: characterization using a fluorescent indicator.

C1 transport in apical membrane vesicles derived from bovine tracheal epithelial cells was studied using the C1-sensitive fluorescent indicator 6-methoxy-N-(3-sulfopropyl) quinolinium. With an inwardly directed 50 mM C1 gradient at 23 degrees C, the initial rate of C1 entry (JC1) was increased significantly from 0.32 +/- 0.

Afferent neural pathways in cough and reflex bronchoconstriction.

Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents. These two reflexes can be evoked both from the larynx and tracheobronchial tree and also from some extrarespiratory sites. Within the airways, certain sites are particularly sensitive to stimulation of cough (larynx and points of proximal airway branching), whereas bronchoconstriction can be triggered from the whole of the tracheobronchial tree.

Lung C-fibre receptor activation and defensive reflexes in anaesthetized cats.

1. With pentobarbitone-anaesthetized cats we have elicited cough reflexes from the tracheobronchial tree and the larynx, and the aspiration and sneeze reflexes from the nasopharynx and the nose respectively. The reflexes were induced by mechanical stimulation of the mucosa, before and during activation of pulmonary C-fibre receptors by intravenous injections of capsaicin or phenylbiguanide.

Comparison of mucus flow rate, radiolabelled glycoprotein output and smooth muscle contraction in the ferret trachea in vitro.

1. The concentration-response curves for rate of mucus output, labelled-glycoprotein output and smooth muscle contraction in response to methacholine, phenylephrine and salbutamol were determined in the ferret trachea in vitro. 2.

Action of a novel drug (Zy 16039) on mucus secretion in the ferret isolated trachea in vitro.

1. The effect of 4-H-2-carboxamido-4-phenyl-thieno-[3,2c]-[1]-benzopyran (Zy 16039) was examined on the smooth muscle contraction, mucus secretion and albumin transudation in the ferret whole trachea in vitro. 2.

Stimulation of Cl secretion by neurokinin A and neurokinin B in canine tracheal epithelium.

We studied the effects of neurokinin A (NKA) and neurokinin B (NKB), the mammalian-derived tachykinins, on the electrical and ion transport properties of canine tracheal epithelium. Both tachykinins dose-dependently increased short-circuit current (Isc) when added to the mucosal (NKA: delta Isc(max) = 24.2 +/- 2.

A novel approach to the ultrastructural localization of cell surface receptors: affinity-gold labeling of Na, K-ATPase.

We describe here a novel method of affinity-gold labeling for the ultrastructural localization and biochemical characterization of functional cell surface receptors. This approach combines the widely used colloidal gold technique, a previously published method for coating the gold with a matrix of derivatized dextran, small receptor-specific ligands, and a photoactivatable cross-linker. The resulting gold-affinity probe directed to a selected receptor by the ligand, is subsequently attached to the receptor by light activation of the cross-linker.

Effect of human eosinophil major basic protein on ion transport in dog tracheal epithelium.

Eosinophil major basic protein (MBP) is a granule-associated cytotoxic protein found in sputum and deposited on airway tissues of patients with acute asthma. We therefore studied the effect of human MBP on ion transport in dog tracheal epithelium. We mounted the posterior tracheal membranes of mongrel dogs in Ussing chambers and measured potential differences across the membranes and short-circuit current.

Cyclic adenosine monophosphate-dependent kinase in cystic fibrosis tracheal epithelium.

Cl-impermeability in cystic fibrosis (CF) tracheal epithelium derives from a deficiency in the beta-adrenergic regulation of apical membrane Cl- channels. To test the possibility that cAMP-dependent kinase is the cause of this deficiency, we assayed this kinase in soluble fractions from cultured airway epithelial cells, including CF human tracheal epithelial cells. Varying levels of cAMP were used in these assays to derive both a Vmax and apparent dissociation constant (Kd) for the enzymes in soluble extracts.

Dose-related effects of pharmacological mediators on tracheal vascular resistance in dogs.

1 Various doses of mediators were tested on tracheal vascular resistance in dogs anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. 2 All drugs produced dose-related changes in vascular resistance.

Vascular actions of airway neuropeptides.

We have studied effects of several neuropeptides perfusing the cranial tracheal arteries bilaterally in anesthetized dogs. All the neuropeptides tested produced dose-related changes in vascular resistance. Substance P and VIP had similar potencies in decreasing tracheal vascular resistance.

Regulation of chloride secretion in dog tracheal epithelium by protein kinase C.

The effects of stimulating protein kinase C on Cl- secretion across dog tracheal epithelium were investigated. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), and the synthetic diacylglycerol, 1-oleolyl-2-acetylglycerol (OAG), which stimulate protein kinase C (PKC), both stimulated short-circuit current (Isc) with Kd of 10 nM and 1 microM, respectively. In Cl(-)-free solution, the increases in Isc were virtually abolished, suggesting that these compounds stimulate Cl- secretion, a hypothesis confirmed for TPA by measurement of 36Cl- fluxes.

The effects of peptides and mediators on mucus secretion rate and smooth muscle tone in the ferret trachea.

The effects of a number of peptides and mediators were measured on the secretion rate of tracheal mucus and tracheal smooth muscle tone in the ferret in vitro whole trachea. The comparison of secretion rate and smooth muscle tone, measured simultaneously in the same preparation, shows that there are wide differences in sensitivity between the two systems; there appears to be no relationship between mucus volume output and smooth muscle contraction. The comparison of mucus secretion rate and glycoprotein output in other models and species to these drugs in the same concentrations indicates that there may be mucus glycoprotein output without an increase in volume output.

The actions of methacholine, phenylephrine, salbutamol and histamine on mucus secretion from the ferret in-vitro trachea.

Methacholine, phenylephrine and histamine produced highly significant and salbutamol significant increases in the rate of mucus secretion from the ferret trachea. Methacholine, phenylephrine and histamine all produced highly significant increases in the rate of output of lysozyme, but the concentration of lysozyme in the mucus was significantly increased only by phenylephrine. Salbutamol produced no significant change in the output of lysozyme, and the concentration of lysozyme in the mucus was significantly decreased.

Chemical control of tracheal vascular resistance in dogs.

With anesthetized dogs we have measured upper tracheal vascular resistance on both sides of the trachea simultaneously by perfusing the cranial tracheal arteries and measuring inflow pressures at constant flows. The ratio of pressure to flow gave vascular resistance (Rtv). Lung airflow, blood pressure (BP), heart rate, and pressure in a cervical tracheal balloon (Ptr) were also measured.