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At least 19 recordsLinked to original sources

PubMed1979

Effect of methacholine chloride on rheology and transport of canine tracheal mucus.

The effect of methacholine chloride (M) on tracheal mucus was investigated in three conscious tracheostomized dogs. Aerosols of M in concentrations of 2--32 mg/ml were delivered intratracheally for 1 min. Mucus was sampled with a cytology brush at 2 min postchallenge and at irregular intervals thereafter. The mechanical properties of each sample were determined in the magnetic microrheometer, and correlated with mucociliary transportability as assayed by the frog palate technique. With high doses of M, there was an increase in volume of secretion collected per unit time. The elastic modulus (G') at 2 min postchallenge went up (to 1.5 x 2.3 x control for 16 and 32 mg/ml, respectively) then fell below control before returning to base line after 30 or 45 min. With low doses of M (2--8 mg/ml) the secretion rate was also above control, but only a decrease in G' (to 0.54 x control) was observed. The decrease in G' at low doses did not significantly alter the frog palate transport rate; however, the increase at higher doses did impede mucociliary transport.

Animals↗

PubMed1975

Chronic cholinergic stimulation of canine respiratory tissue. Its effect on the activities of glycosyltransferases and release of macromolecules.

The influence of cholingergic stimulation on the incorporation of D-[6-3H]glucosamine into macromolecules released by canine trachea in vitro, and the capacity of subcellular fraction of this tissue to catalyze the transfer of various sugars to specific glycoproteins were measured. Canine trachea was incubated with radiohexosamine for 18 hours in the presence of methacholine chloride. The [3H]macromolecules subsequently released were fractionated on columns of 1 per cent agarose. Those macromolecules eluted from the columns with a mobility identical to that of large molecular weight, mucin-type glycoproteins of canine tracheal pouch secretions collected in vivo were increased. The tissue then did not respond to further challenges with acetylcholine chloride, at least as regards the release of radiomacromolecular. In addition, in vitro challenges of methacholine chloride failed to alter the specific activities of the tracheobronchial tissue glycosyltransferases. The specific activities of 2 galactosyltransferases, a sialytransferase, and an N-acetylgalactosaminyltransferase were elevated after 1 month and after 2 months of daily subcutaneous injections of methacholine chloride. No further increases were seen during the third month of injections; throughout the 3 months, the specific activity of fucosyltransferase failed to change.

Acetylcholine↗

PubMed1990

Inflation of antishock trousers increases bronchial response to methacholine in healthy subjects.

We studied changes in lung volumes and in bronchial response to methacholine chloride (MC) challenge when antishock trousers (AST) were inflated at venous occlusion pressure in healthy subjects in the standing posture, a maneuver known to shift blood toward lung vessels. On inflation of bladders isolated to lower limbs, lung volumes did not change but bronchial response to MC increased, as evidenced by a greater fall in the forced expiratory volume in 1 s (FEV1) at the highest dose of MC used compared with control without AST inflation (delta FEV1 = 0.94 +/- 0.40 vs. 0.66 +/- 0.46 liter, P less than 0.001). Full inflation of AST, i.e., lower limb and abdominal bladder inflated, significantly reduced vital capacity (P less than 0.001), functional residual capacity (P less than 0.01), and FEV1 (P less than 0.01) and enhanced the bronchial response to MC challenge compared with partial AST inflation (delta FEV1 = 1.28 +/- 0.47 liter, P less than 0.05). Because there was no significant reduction of lung volumes on partial AST inflation, the enhanced bronchial response to MC cannot be explained solely by changes in base-line lung volumes. An alternative explanation might be a congestion and/or edema of the airway wall on AST inflation. Therefore, to investigate further the mechanism of the increased bronchial response to MC, we pretreated the subjects with the inhaled alpha 1-adrenergic agonist methoxamine, which has both direct bronchoconstrictor and bronchial vasoconstrictor effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.

Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.

Adult↗

PubMed1991

Muscarinic modulation of the vasodilatory effects of vasoactive intestinal peptide at the rat thyroid gland.

In the thyroid gland, vasoactive intestinal peptide (VIP) and acetylcholine (ACh) are found in nerve fibers associated with secretory cells and blood vessels. We have, therefore, initiated studies to explore the actions of and interactions between cholinergic agents and VIP in the regulation of thyroid vascular conductance (VC). Thyroid and other organ blood flows were measured using radiolabelled (141Ce) microspheres injected directly into the left cardiac ventricle of anesthetized male rats. The mean systemic arterial pressure was monitored and used in the calculation of organ VC (blood flow/arterial pressure). Plasma TSH, T3, and T4 levels before and after infusions were measured by RIA. The acute administration of ACh (3 x 10(-8) mol/100 g BW) over 4 min increased thyroid VC, whereas nicotine (10(-7) mol/100 g BW) had no such effect. Circulating TSH and thyroid-hormone levels following ACh or nicotine were not different from those in vehicle-treated animals at 20 min or 2 h after infusion. This observation suggested that ACh acts through muscarinic receptors at the thyroid gland to increase VC. In order to extend these observations and to evaluate whether VIP might exert any of its thyroidal effects on VC via muscarinic receptors, we assessed the effects of ACh, methacholine chloride (MCC), and VIP in the presence and absence of the muscarinic receptor blocker atropine. Rats were treated intravenously with saline or atropine (3 mg/kg) 20 min before intravenous infusions of vehicle, ACh (3 x 10(-8) mol/100 g BW), MCC (5 x 10(-9) mol/100 g BW), or VIP (10(-11) mol/100 g BW).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1991

[Local effect of calcitonin gene-related peptide on human sweat gland function].

The effect of local administration of calcitonin gene-related peptide (CGRP) on sweating activity was evaluated on normal human volunteers. CGRP and methacholine chloride (MCH) was dissolved in 0.1 ml of 0.9% NaCl solution to a specified concentration, and was injected intradermally at the center of a 1.3 cm2 forearm test area. The sweat rate was recorded continuously by capacitance hygrometry in a relatively cool environment (Ta, 23 degrees C). CGRP did not elicit any sweat secretion when administrated by alone, but significantly increased the sweat rate when it was administrated with MCH. The maximum enhancement of MCH-induced sweating by CGRP was observed at a concentration of 10(-5) g/ml of CGRP. There was clear dose-dependent relationship between the dose of CGRP and its enhancement. Recently, CGRP-like immunoreactivity is demonstrated to be present in cholinergic nerve terminals around the human sweat glands. These observations have strongly suggested that CGRP enhances the cholinergic sweating activity. Although the underlying mechanism is still obscure, CGRP may enhance the sweating as a consequence of vasodilation which has been known to be a major activity of CGRP. As for the evaluation of human sweat gland function, CGRP-induced peptidergic regulation should be considered as well as cholinergic regulation.

Acetylcholine↗

PubMed1977

Gastric secretory and motility studies in chronic chagasic patients.

In Chagas' disease, the degeneration of the nerve cells of the intramural parasympathetic ganglia of the stomach causes a wide range of motor and secretory disturbances of the organ. To assess and to correlate the alterations of these two gastric functions, electromanometric and secretory studies were performed in 22 chagasic patients and in 12 control individuals. The gastric antrum electromanometric records were carried out in basal conditions and under the stimulation of methacholine chloride (Mecholyl). Gastric secretory studies were carried out in two sessions with a Kay's test: in the first, with the test alone; in the second, associated with bethanechol chloride (Urecholine). The chagasic patients were divided into two groups according to their gastric motor response to methacholine. It was concluded that the parasympathetic denervation in Chagas' disease changes both acid and pepsin secretions in the same direction but that as the disease worsens, the responsiveness of pepsin secretion to cholinergic action tends to disappear earlier than that of acid secretion.

Adult↗

PubMed1977

Abnormal vascular reactions in atopic dermatitis.

Vascular reactions to mechanical stroking, topical application of nicotinic acid ester, and methacholine chloride were examined in both the normal and abnormal skin of 100 patients with atopic dermatitis and 20 patients with allergic contact dermatitis. White dermographism, nicotinic acid blanching, and delayed blanch with methacholine consistently occurred in areas of skin with eczematous change of patients with atopic dermatitis and those with allergic contact dermatitis. Normal skin of atopic patients did not show the abnormal vascular reactions. It is suggested that white dermographism, nicotinic acid blanching, and delayed blanch with methacholine seen in atopic dermatitis are secondary phenomena that give no definite information concerning the diagnosis of this disease.

Adult↗

PubMed1976

Cromolyn therapy in patients with bronchial asthma. Effect on inhalation challenge with allergen, histamine, and methacholine.

The action mechanism of cromolyn sodium and its effect on bronchial sensitivity to allergen, methacholine chloride, and histamine inhalations were studied in 17 asthmatic subjects. Cromolyn capsules or placebo was administered by an inhaler (Spinhaler) randomly on alternate days 30 minutes before aerosol challenge. Cromolyn and placebo did not differ in their effect on bronchial response to histamine or methacholine. However, the degree of decrease in forced vital capacity and forced expiratory volume in one second after allergen challenge was significantly reduced by cromolyn in 15 of 17 subjects. Immediate and delayed reactions of itching, tightness, or wheezing developed in 14 subjects after allergen challenges following placebo intake and were prevented or substantially inhibited by cromolyn.

Adolescent↗

PubMed1975

Myotonic pupils in Charcot-Marie-Tooth disease. Successful relief of symptoms with 0.025% pilocarpine.

Twenty-seven members of a family with dominantly inherited Charcot-Marie-Tooth disease (CMTD) were examined. Fifteen members had CMTD and 13 of these had varying amounts of myotonic pupillary abnormalities similar in some ways to Adie tonic pupil syndrome. Those with graver neurologic disease showed greater pupillary abnormalities. Ten of the 15 patients had pupillary constriction with methacholine chloride (Mecholyl) and some of these had extensive iris atrophy. Several affected patients received symptomatic relief from 0.025% pilocarpine. Seven other patients with CMTD who were not related to our initial family were checked for myotonic pupils; two had findings similar to our initial family. Pupillary abnormalities in certain patients with CMTD appear secondary to a parasympathetic denervation of the iris sphincter and ciliary muscle, as shown by a positive methacholine test, and probably represent part of the autonomic nervous system dysfunction associated with the polyneuropathy in CMTD.

Adult↗

PubMed1990

Factors related to the nocturnal worsening of asthma.

The nocturnal worsening of asthma is a very common problem, yet little is known about the relationships between the nocturnal worsening and daytime lung function, methacholine bronchial responsiveness, the degree of the circadian variability in bronchial responsivity, and the nocturnal sleep pattern. This study demonstrates in 20 asthmatic patients that the overnight fall in the peak expiratory flow rates (PEFR) is related to the severity of daytime airflow limitation (r = 0.73, p less than 0.001) and daytime bronchial responsiveness (r = 0.48, p less than 0.05). In individuals with larger overnight decrements in PEFR, bronchial responsivity at 0400 h is so great that normal saline inhalation alone can produce a greater than 20% fall in the FEV1. Sleep quality and sleep staging are not correlated to the change in the PEFR. Thus, the overnight decrement in asthmatic lung function is related to the daytime severity of asthma as determined by daytime measurements of airflow limitation and bronchial responsiveness as well as the circadian variation in bronchial responsivity.

Adult↗

PubMed1988

Peripheral type benzodiazepine receptor and airway smooth muscle relaxation.

It has been postulated that a benzodiazepine receptor with a micromolar affinity may be associated with Ca++ channels in peripheral organs. We examined the actions of Ro5-4684 (parachlorodiazepam) and midazolam on guinea pig tracheal smooth muscle contraction. Binding studies using [3H]Ro5-4684 indicate the presence of a "peripheral" type binding site with a Kd of approximately 4 nM and maximum binding of 1 pmol/mg of protein. Midazolam did not displace radioligand. In tension studies no activity was seen for Ro5-4684 or midazolam at concentrations below 1 microM. Higher concentrations relaxed the airway smooth muscle under basal tone, the effect was augmented significantly by epithelium removal. Similar results were obtained in tissues precontracted with methacholine or KCl. Midazolam (1 or 100 microM) significantly (P less than .05) attenuated the response to Ca++ in K+-depolarized tracheal strips, the effect was greater at low Ca++ concentrations. The compounds appear to function as Ca++ antagonists in airway smooth muscle but ar not typical as shown by their ability to reduce basal tone in airway smooth muscle.

Animals↗

PubMed1977

Role of the parasympathetic system in antigen-induced bronchospasm.

Human subjects, sensitive to ragweed, inhaled aerosols of increasing concentrations of ragweed pollen extract in the presence and absence of pretreatment with inhaled atropine. The cumulative dose of antigen required for a 35% decrease in airways conductance was termed PD35. Atropine, 1.2 or 5 mg, increased airways conductance before antigenic challenge but did not alter signigicantly the PD35 for ragweed extract, although these doses of atropine inhibited airways responses to inhaled methacholine chloride and citric acid. We conclude that the cholinergic nervous system plays a modulating role in bronchomotor tone and responses to irritants, but that parasympathetic reflexes are not invariably a major component of human bronchial responses to inhaled allergen.

Airway Resistance↗

PubMed1976

Pharmacological assessment of 3-tert-butylsydnone.

The pharmacological effects of the mesoionic derivative, 3-tert-butylsydnone, were investigated. Administration to rats caused clonic convulsions. The CD50 of 3-tert-butylsydnone was 0.471 +/- 0.033 mmole/kg. Trimethadione, but not phenytoin sodium or proadifen hydrochloride, protected the rat from the effects of 3-tert-butylsydnone. After administration of this compound, pentobarbital sodium sleeping time was reduced in the rat, but blood pressure and ECG were unchanged in the dog. Pretreatment of the mouse with 3-tert-butylsydnone did not influence the LD50 of epinephrine hydrochloride. The action of methacholine chloride in the rat was not blocked, and the pupil of the rabbit eye was unaffected. Tests for analgesic and oxytocic activity were negative. Chronic administration of a small dose to the rat for 70 days had no effect on blood glucose, blood urea nitrogen, hemoglobin, or microhematocrit values.

Anesthesia↗

PubMed1978

Tracheobronchial secretions collected from intact dogs. II. Effects of cholinomimetic stimulation.

The effect of cholinomimetic stimulation on the quantity and composition of tracheobronchial secretions (TBS) collected from intact dogs was studied. After the administration of methacholine chloride, the collection rate of TBS increased over threefold within 10 min and returned to the control level by 50 min. Even though there was an increase in the total amount of protein collected, the protein concentration of the secretions decreased initially by 40%, returning to normal by 30 min. This was the result of an apparent dilution of the secretions by nonproteinaceous components. In addition, at 10 min, there was an increase in the protein associated with mucins. These responses were blocked by the preadministration of atropine. When TBS was separated into supernatant and pellet phases by centrifugation, we found that, following methacholine, there was a 35% increase in the ratio of albumin to IgG in the supernatant phase. These results suggest that the increased secretion due to methacholine may result, in part, by a selective filtration of fluid from the interstitial and/or vascular compartment(s) with proteins appearing in the secretory mixture based partially on their size.

Animals↗

PubMed1975

Enzyme secretion in the absense of zymogen granules.

Pure pancreatic juice was collected from the cannulated common bile duct of anesthetized rats after an overnight fast. Digestive enzyme secretion was followed in these animals during and after the progressive degranulation of acinar cells produced by sequentially applied cholinergic stimuli. The kinetics of degranulation, a progressive decrease in the number of zymogen granules in acinar cells, was estimated from the relative cell volume occupied by electron-opaque granules at various times using a random pointcount stereological technique to examine tissue sections. Three hourly injections of methacholine chloride were sufficient to produce the almost complete disappearance of electron-opaque granules from secretory cells. Greatly augmented enzyme secretion was still observed in their absence, 7-25 times greater than control values: 10-fold for protein output overall, 7-fold for trypsinogen, and 25-fold for chymotrypsinogen. Secretion in the absence of zymogen granules is discussed relativeto exocytosis and three-compartment (intracellular storage, cytoplasm, and duct lumen)secretory models.

Animals↗

PubMed1977

Uropharmacology: v. choline esters and other parasympathomimetic drugs.

Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response.

Animals↗

PubMed1992

In vivo evaluation of airway and pulmonary tissue response to inhaled methacholine in the rat.

The current study was designed to assess the methacholine dose-response behaviour of the airways and pulmonary parenchyma with the aid of alveolar capsules. The experiments were performed in eight adult female Wistar rats (155-250 g). The animals were anaesthetized with sodium pentobarbital (30 mg kg-1 i.p.) and mechanically ventilated. Measurements of tracheal (ptr) and alveolar (pA) pressures and the pressure change across the airway (p(aw)) were performed prior to and after exposing rats to aerosols generated from sequentially increasing concentrations of methacholine chloride solution (2, 4, 8, 16, 32, 64 and 128 mg ml-1) through the breathing circuit. Baseline p(aw) and pA mean (+/- SD) values (6.44 +/- 2.06 and 8.25 +/- 3.44 cmH2O, respectively) were not statistically different (P = 0.220). The increases in ptr and pA were significant during the dose-response study (P = 0.001), whereas p(aw) was not increased. The increase in pA was significantly higher than that of p(aw) (P less than 0.001). The relationship between the mean (+/- SE) values of ptr and pA could be well described by a straight line (r = 0.990, P less than 0.001). There were also significant correlations based on regression equations between ptr and p(aw) (r = 0.947, P less than 0.001) and pA and p(aw) (r = 0.913, P = 0.004). These findings suggest that the pulmonary tissue of rats is a major component responsible for the increase in lung impedance observed after methacholine challenge. In addition, airway and pulmonary parenchyma pressure changes were correlated, suggesting that both lung regions have a similar sensitivity to the agonist. Our results indicate that the response of peripheral tissues should be considered during bronchial challenge protocols in rats.

Administration, Inhalation↗