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Biomedical subjects

S E Webber

Publications and source records attributed to S E Webber.

At least 73 records · Page 4Linked to original sources
PubMed1989

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. In control conditions, when mucus secretion was not stimulated by drugs, the concentration of albumin in the lumen was over half that in the buffer, and about six times greater than those of the two dextrans. 3. Methacholine and phenylephrine caused large increases in mucus secretion and albumin output and decreases in albumin concentration. The responses were proportional to drug concentration. We concluded that albumin output is increased but diluted with submucosal gland secretion. 4. Salbutamol caused a small increase in mucus secretion and large increases in output and concentration of albumin. The concentration of albumin became greater than that in the external buffer medium. The responses were proportional to concentration of salbutamol. 5. Histamine increased mucus secretion and albumin output and concentration. 6. None of the four drugs increased the output of dextran-70,000. Methacholine and phenylephrine increased the output of dextran-9000, but to a far less extent than for albumin. 7. Cooling the trachea and buffer to 4 degrees C almost abolished the stimulation of mucus and albumin outputs due to methacholine. 8. Increasing the concentration of albumin external to the trachea did not proportionally increase albumin secretion, the logarithmic relationship suggesting saturation of an active transport system. 9. We conclude that albumin is secreted by active transport into the tracheal lumen, and that the rate of transport can be augmented by salbutamol to build up a higher concentration in the lumen than in the external buffer.

Albuterol↗
PubMed1989

Cold and hyperosmolar fluids in canine trachea: vascular and smooth muscle tone and albumin flux.

We have studied the effects of liquids of various osmolalities and temperatures on the tracheal vasculature, smooth muscle tone, and transepithelial albumin flux. In 10 anesthetized dogs a 10- to 13-cm length of cervical trachea was cannulated to allow instillation of fluids into its lumen. The cranial tracheal arteries were perfused at constant flow, with monitoring of the perfusion pressures (Ptr) and the external tracheal diameter (Dtr). Control fluid was Krebs-Henseleit solution (KH) with NaCl added to result in a 325-mosM solution (isotonic). Hypertonic solutions were KH with NaCl (warm hypertonic) or glucose (hypertonic glucose) added to result in a 800-mosM solution. All solutions were at 38 degrees C, with isotonic and the hypertonic NaCl solutions also given at 18 degrees C (cold isotonic and cold hypertonic). Fluorescent labeled albumin was given intravenously, and the change in fluorescence in the fluid was measured during each 15-min period. Changing from warm isotonic to cold isotonic decreased Dtr and Ptr. Changing from warm isotonic to warm hypertonic or hypertonic glucose decreased Ptr with no change in Dtr. The cold hypertonic responses were not different from cold isotonic responses. Warm hypertonic solution increased albumin flux into the tracheal lumen over a 15-min period to three times that of the control period, persisting for 15 min after replacement with warm isotonic solution. Cooling induces a vasodilation and smooth muscle contraction of the trachea, whereas hypertonic solutions result in vasodilation and, if osmolality is increased with NaCl, an increase in albumin flux into the tracheal lumen.

Animals↗
PubMed1989

Electrolyte and other chemical concentrations in tracheal airway surface liquid and mucus.

With the ferret in vitro tracheal preparation, we measured the electrolyte and chemical composition of airway surface liquid (ASL) under control conditions and when drugs were added to promote submucosal gland secretion and to change epithelial ion transport. Control ASL was hyperosmolar (342 +/- 2.8 mosmol/kg) compared with ferret plasma and surrounding buffer. Higher values were also found for sodium (167 +/- 1.7 mmol/l), potassium (9.0 +/- 0.05 mmol/l), total calcium (3.46 +/- 0.11 mmol/l), and ionized calcium (2.55 +/- 0.18 mmol/l). pH was lower (7.12 +/- 0.03) than in plasma or buffer. Addition of methacholine to the surrounding buffer increased flow of ASL and potential difference across the mucosa and lowered pH, calcium, sodium, and chloride concentrations. Potassium concentration was increased. Phenylephrine increased flow and decreased calcium concentrations. Salbutamol (albuterol) had no effect on flow but decreased pH and increased calcium and potassium concentrations. Histamine increased flow and calcium concentrations and decreased pH. These changes are presumably due to changes in gland secretion and epithelial transport. Methacholine and phenylephrine increased the sugar content of the secretions, the changes with phenylephrine being larger. Thus resting ASL is hyperosmolar and relatively acid, with high cation contents, and administration of drugs changes its composition by actions on submucosal glands and epithelium.

Animals↗
PubMed1989

Effects of antigen on tracheal circulation and smooth muscle in sheep of different ages.

The effects of Ascaris suum antigen on tracheal circulation and tracheal smooth muscle tone were compared in two groups of sheep: the first group was 1 yr old (14 sheep) and the second 5 yr old (8 sheep). Cranial tracheal arteries of anesthetized and paralyzed sheep were perfused at constant flow with monitoring of perfusion pressure. Tracheal smooth muscle tone was assessed by measuring changes in the external diameter of the cranial trachea. Close-arterial injection of antigen (1-20 micrograms) in young sheep produced dose-dependent vasodilation (6.1-15.5% fall in perfusion pressure) and smooth muscle contraction (0.06-0.28 mm reduction in tracheal diam). In old sheep, antigen (1-20 micrograms) produced vasoconstriction (4.1-16.8%) but no smooth muscle response. The smooth muscle contraction in young sheep was blocked by mepyramine (2 mg/kg iv) suggesting mediation by release of histamine. The vasodilation in young sheep and the vasoconstriction in old sheep were reduced by indomethacin (5 mg/kg iv), and the residual response was further reduced by FPL 55712 (2 mg/kg iv), suggesting mediation by both cyclooxygenase products and leukotrienes. Thus antigen given in the tracheal vasculature releases a mixture of inflammatory mediators. This mixture of mediators or their actions on the tracheal vasculature and smooth muscle may depend on the age of the sheep.

Age Factors↗
PubMed1989

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. The vessels have thin walls formed by a single layer of flattened endothelium with tight junctions and without pericytes or smooth muscle cells. Characteristically the sinuses lie between the cartilage and lamina propria of the trachea or between cartilage and smooth muscle in the bronchi. Sinuses of greater than 50 microns transverse diameter are not found in airways less than 1.0 mm across.

Animals↗
PubMed1988

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. Zy 16039 (0.1-20 microM) produced a concentration-dependent relaxation of the ferret trachea contracted by methacholine (1 microM) and phenylephrine (10 microM). The relaxations were about 20% of the full contractions. 3. Zy 16039 has no effect on the resting (zero) output of mucus in the ferret trachea. Methacholine-induced mucus secretion was significantly inhibited by Zy 16039, whereas phenylephrine-induced secretion was significantly increased. 4. Methacholine-induced secretion of lysozyme, a marker of serous cell secretion, was inhibited by Zy 16039 both with regard to output and concentration of lysozyme. In contrast, Zy 16039 significantly increased the output of lysozyme due to phenylephrine, with no effect on concentration. 5. Zy 16039 had no significant effect on the rate of output of fluorescent albumin through the tracheal wall. However the concentration of albumin in the mucus samples was changed because of the effect of Zy 16039 on mucus secretion induced by methacholine and phenylephrine. 6. We conclude that Zy 16039 relaxes airway smooth muscle, and either promotes or inhibits mucus secretion depending on its source. It has qualitatively similar actions to vasoactive intestinal peptide.

Albumins↗
PubMed1988

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. Changes in tracheal smooth muscle tone were also measured. 2. Histamine and SKF 71481-A2 contracted the tracheal smooth muscle and this effect was blocked by the H1-antagonist mepyramine. Stimulation of H2-receptors with dimaprit had no effect on tracheal smooth muscle tone. 3. Histamine had a complex action on the tracheal vasculature producing either a triphasic change (early dilatation then constriction followed by late dilatation) or just a constriction. SKF 71481-A2 always produced a biphasic change in vascular resistance (dilatation followed by constriction). Dimaprit dilated the tracheal vasculature. 4. The late dilatation produced by histamine in some sheep was blocked by bilateral cervical vagotomy but the mechanism for this effect is not known. No other responses to histamine, SKF 71481-A2 or dimaprit were affected by vagotomy. 5. The vasoconstriction produced by histamine and SKF 71481-A2 was antagonized by mepyramine indicating a H1-receptor-mediated effect. Cimetidine had no effect on the vasoconstriction to histamine suggesting a lack of involvement of H2-receptors. 6. The vasodilatation produced by histamine and SKF 71481-A2 was also antagonized by mepyramine, again suggesting a H1-receptor-mediated action. Cimetidine had no effect on the vasodilator response to histamine indicating no involvement of H2-receptors in this response. 7. The dilator effect of dimaprit was antagonized by cimetidine suggesting this effect was mediated by H2-receptors. 8. We conclude that H1-receptors in the various parts of the sheep tracheal vasculature can cause increases and decreases in total tracheal vascular resistance; that H2-receptors decrease resistance; and that the tracheal smooth muscle contracts on activation of H1-receptors but has no response to H2-agonists.

Animals↗
PubMed1988

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. 2. Neurokinin A (NKA, 0.02-20 pmol), calcitonin gene-related peptide (CGRP, 2-200 pmol) and peptide histidine isoleucine (PHI, 0.02-2 nmol) dose-dependently decreased tracheal vascular resistance (Rtv). NKA was 10 and 100 times more potent than CGRP and PHI, respectively. The duration of the response to CGRP was greatly prolonged with larger doses. Galanin (0.2-2 nmol) had no appreciable effect on Rtv. 3. Neuropeptide Y (NPY 0.02-2 nmol) and bombesin (0.02-10 nmol) dose-dependently increased Rtv. However, the dose-response curve for bombesin was bell-shaped suggesting the development of tachyphylaxis with larger doses. In smaller doses, bombesin was twice as potent as NPY. The duration of the response to NPY was prolonged with larger doses. 4. With the exception of PHI no neuropeptide altered tracheal smooth muscle tone; PHI (1 and 2 nmol) caused small dilatations of the trachea. 5. The effects of capsaicin (2-100 nmol) were complex. Usually, the vascular response had two dose-dependent phases: a rapid vasoconstriction followed by a small, longer-lasting vasodilatation. The tracheal smooth muscle response was usually biphasic, a contraction followed by a relaxation. 6. According to previous and present data, the order of potency of the neuropeptides on the canine tracheal vasculature is for the vasodilators : NKA > vasoactive intestinal peptide (VIP) > CGRP > substance P > PHI, and for the vasoconstrictors: bombesin > NPY. The longer-acting neuropeptides (VIP, CGRP and NPY) may be more important than the shorter-acting neuropeptides (substance P, NKA, PHI and bombesin) as regulators of the airway wall blood flow.

Animals↗
PubMed1988

The effects of peptide histidine isoleucine and neuropeptide Y on mucus volume output from the ferret trachea.

1. The effects of peptide histidine isoleucine (PHI) and neuropeptide Y (NPY) were examined on the mucus volume output produced by methacholine and phenylephrine in the ferret whole trachea in vitro. 2. Sustained application of methacholine (5 microM) or phenylephrine (20 microM) produced a maintained volume output of mucus from the trachea. Both these agonists also increased the output of lysozyme (a marker for serous cell secretion). 3. PHI inhibited the maintained mucus volume output produced by methacholine but had no effect on that due to phenylephrine. The output of lysozyme produced by methacholine or phenylephrine was not significantly changed by PHI. 4. NPY enhanced the volume output of mucus produced by methacholine or phenylephrine; however, the rate of output of lysozyme in mucus produced by both agonists was reduced by NPY. 5. We suggest that PHI has no effect on serous cell secretion but inhibits secretion from another source, possibly mucous cells. NPY inhibits serous cell secretion but has a stronger stimulant action on secretion from another source, again possibly mucous cells. 6. PHI and NPY may be important physiological modulators of mucus volume output in the ferret trachea.

Animals↗
PubMed1988

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. 2. During the 20-30 s apnoea due to C-fibre stimulation, the cough reflex from both sites and the sneeze reflex were completely abolished, whereas the aspiration reflex response was approximately halved. Reflex contractions of genioglossus muscle still occurred at this time, but were far weaker than in the control state. 3. During the rapid shallow breathing that immediately followed apnoea due to C-fibre receptor stimulation, the defensive reflexes recovered: the aspiration and sneeze reflexes fully and the cough reflexes to about half of the control response. 4. Acute hypotension due to haemorrhage, of a size considerably greater than that due to stimulation of the pulmonary C-fibre receptors, caused no significant inhibition of the cough reflex from the tracheobronchial tree. 5. We conclude that the pulmonary C-fibre reflex powerfully inhibits airway defensive reflexes, and that its activation is unlikely to contribute positively to coughing induced by aerosols of capsaicin and similar agents.

Action Potentials↗
PubMed1987

Lipoxin A-induced inhibition of human natural killer cell cytotoxicity: studies on stereospecificity of inhibition and mode of action.

Human leukocyte-derived lipoxin A (LXA; 5S,-6R,15S-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid) inhibits the cytotoxic activity of human natural killer (NK) cells. LXA and three of its isomers were prepared by total organic synthesis and assayed for activity with human NK cells. Dose-response studies showed that biologically derived LXA and synthetic LXA were equally effective in inhibiting NK cell cytotoxicity. 6S-LXA, with its 6S-OH group in an (S) configuration, proved to be approximately half as potent as LXA. In contrast, 6S-11-trans-LXA and 11-trans-LXA displayed virtually no inhibitory activities. The methyl esters of both LXA and 6S-LXA proved to be more potent than their corresponding free acids. Thus, LXA inhibition of NK cells displays clear-cut stereochemistry. In the absence of putative inhibitors, NK cells bind to their targets to form conjugates. This event is followed by polarization of the NK Golgi apparatus, which moves towards the plasma membrane that is in contact with the target cell. However, in the presence of either the methyl ester or free acid of LXA, the Golgi apparati of NK cells bound to their targets were randomly oriented. In contrast, neither 6S-11-trans-LXA nor the potent NK inhibitor prostaglandin E2 affected the polarization. Furthermore, although prostaglandin E2 resulted in a decrease in NK-target cell binding efficiency, LXA and its isomers failed to affect conjugate formation. Together these results indicate that LXA-induced inhibition of NK cytotoxicity does not act on NK cell binding but may block cytotoxicity by disrupting "signals" involved in the specific orientation of the Golgi. Thus, this latter event may appear to be important in cytotoxicity.

Cell Aggregation↗
PubMed1987

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. It is concluded that methacholine, phenylephrine and histamine are potent stimulators of serous cell secretion whereas salbutamol has only a weak secretory action on these cells. Methacholine, histamine and salbutamol probably stimulate secretion from mucous cells as well as from serous cells. The increase in the concentration of lysozyme produced by phenylephrine may be due to stimulation of a fluid reabsorption mechanism.

Albuterol↗
PubMed1987

The effect of vasoactive intestinal peptide on smooth muscle tone and mucus secretion from the ferret trachea.

The effect of vasoactive intestinal peptide (VIP) was examined on the smooth muscle contraction and mucus secretion produced by methacholine and phenylephrine in the ferret whole trachea in vitro. VIP (0.5 to 800 nM) produced a concentration-dependent relaxation of the ferret trachea contracted by methacholine (1 microM) and phenylephrine (10 microM). The concentration-response curves for methacholine- and phenylephrine-induced contractions were both shifted to the right by VIP (0.1 microM). Methacholine-induced secretion was inhibited in a concentration-dependent manner by VIP, whereas that due to phenylephrine was enhanced. The concentration-response curve for methacholine-induced secretion was shifted to the right by VIP, whereas the curve for phenylephrine was shifted to the left. Methacholine produced a concentration-dependent increase in the rate of output of lysozyme from the ferret trachea with no corresponding increase in the concentration of lysozyme in the mucus. Phenylephrine produced a concentration-dependent increase in the rate of output and in the concentration of lysozyme. VIP (0.1 microM) significantly increased the concentration of lysozyme in the mucus produced by methacholine with no increase in the rate of lysozyme output. However, the rate of lysozyme output due to phenylephrine was significantly increased by VIP (0.1 microM) with no increase in concentration. We suggest that VIP inhibits secretion from mucous cells stimulated by methacholine, and enhances the secretion produced by phenylephrine from serous cells.

Animals↗
PubMed1987

Lung and cardiac reflex actions on the tracheal vasculature in anaesthetized dogs.

1. With pentobarbitone-anaesthetized dogs, the cranial tracheal arteries have been independently perfused on both sides, to measure vascular resistance. Blood pressure and contractions of tracheal muscle were also measured. 2. Capsaicin was injected intravenously to stimulate lung C-fibre receptors. In breathing and in paralysed artificially ventilated dogs it decreased tracheal vascular resistance and blood pressure, and contracted tracheal muscle. The effects were abolished or far smaller after bilateral cervical vagosympathectomy. 3. Veratrine was injected intravenously to stimulate slowly adapting pulmonary stretch receptors and cardiac receptors. In breathing and in artificially ventilated dogs it lowered tracheal vascular resistance and blood pressure, and had variable effects on tracheal muscle tone. The vascular effects were prevented by vagotomy. 4. Veratrine injected into the left atrium caused similar vascular changes to intravenous administration. The changes were prevented by vagotomy. Veratrine causes a tracheal vasodilatation by action on cardiac receptors. 5. Inflation of the lungs in artificially ventilated dogs, to stimulate slowly adapting pulmonary stretch receptors, had no effect on tracheal vascular resistance but decreased blood pressure and tracheal muscle tone, the latter being prevented by vagotomy. 6. Bilateral carotid arterial occlusion, to decrease the discharge in carotid sinus baroreceptors, had no effect on tracheal vascular resistance but increased blood pressure and contracted tracheal muscle, the last two responses being greatly reduced by cutting the sinus nerves. 7. It is concluded that stimulation of lung C-fibre and cardiac receptors causes a reflex tracheal vasodilatation, but that no changes in the tracheal vascular bed occur with stimulation of slowly adapting pulmonary stretch receptors or inhibition of carotid sinus baroreceptors.

Anesthesia, General↗
PubMed1987

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. In paralyzed dogs, systemic hypoxia due to artificial ventilation with 10% O2-90% N2 increased Rtv by +8.1 +/- 1.0% (SE), Ptr by +76 +/- 22.8%, and BP by +18.9 +/- 24%. After bilateral cervical vagosympathectomy the increases in Rtv and BP were present (+8.8 +/- 0.9 and +22.3 +/- 0.3%, respectively). After carotid body denervation Rtv, Ptr, and BP increased (+6.4 +/- 1.3, +58.6 +/- 31.6, and +14.6 +/- 3.3%, respectively). After vagotomy Rtv and BP increased (+14.1 +/- 1.7 and +22.4 +/- 10.1%, respectively). Tracheal perfusion with hypoxic blood caused a small vasodilation (-2.2 +/- 1.1%). Systemic hypercapnia due to artificial ventilation with 8% CO2-92% air increased Rtv by +16.7 +/- 3.8%, Ptr by +67 +/- 2.0%, and BP by +12.9 +/- 9.9%. Tracheal perfusion with hypercapnic blood caused a small vasodilation (-2.5 +/- 1.2%). Stimulation of the carotid body chemoreceptors with KCN caused a small increase in Rtv (+1.2 +/- 0.5%) and increases in Ptr (+49.8 +/- 13.6%) and BP (+11.1 +/- 2.1%). Systemic hypoxia and hypercapnia caused tracheal vasoconstriction mainly by an action on the central nervous system.

Animals↗