SEARCH · PubMed Health

Results for “Methacholine Chloride”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed1983

Regional ionic and albumin content of fluid in the tracheobronchial tree in dogs.

We have devised a technique for collecting airway fluid from the bronchi in order to investigate the biochemical indices of airway fluid in normal dogs and the changes produced in them by pharmacological interventions. We collected airway fluid from the trachea by a screen technique and by means of filter paper cylinders inserted through a fiberoptic bronchoscope (the new method) and from main and segmental bronchi by the new method only. When bronchial fluid was compared with plasma, the concn of albumin was found to be much lower, Na+ lower, and Cl- either higher or similar. The Na+:Cl- ratio was lowest in fluid from the trachea (1.04) and highest in fluid from segmental bronchi (1.14), but was significantly lower at all levels than in plasma (1.32). Subcutaneous administration of methacholine chloride significantly increased the weight of airway fluid collections. Infusion of 5% hypertonic saline induced changes in the concns of electrolytes (but not of albumin) that correlated with changes in the plasma. The major differences in electrolyte and albumin concns in airway fluid and plasma likely reflect a bidirectional transepithelial flux of these ions. The regional differences in electrolyte concns and ratios may be due to differences in anatomic structure and in the functioning of ionic pumps along the tracheobronchial tree.

Albumins↗

PubMed1987

Parasympathetic denervation hypersensitivity of the iris in ocular hypertension.

Seventy-eight ocular hypertensive patients and 47 age-and sex-matched control subjects were assessed for parasympathetic denervation hypersensitivity of the iris using topical application of 2.5% methacholine chloride solution. Constriction of the pupil in response to methacholine stimulation of the sphincter pupillae was significantly greater in the ocular hypertensive patients than the control group (P less than 0.001). The implications are discussed, with particular reference to the association between autonomic neuropathy and the primary glaucomas.

Administration, Topical↗

PubMed2000

[Pharmaceutical contribution to the non specific challenge in bronchial provocation tests].

Aerosols of methacholine chloride are used in inhalation tests to measure non-specific bronchial responsiveness. Inhalation challenge solutions are not commercially available neither by pharmaceutical industry nor in France by the PCH-APHP. To reply to doctor's request, dilute concentrations of methacholine must be prepared properly in order to protect the patient and to assure doctor of test reproductibility. Osmolarity, pH and degradation of different dilute concentration of methacholine chloride have been compared with two diluents. This study allowed us to validate our preparation of solutions.

Administration, Inhalation↗

PubMed1994

Modulatory effects of calcitonin gene-related peptide and substance P on human cholinergic sweat secretion.

Immunoreactivity to various peptides has been demonstrated in nerve terminals around the sweat glands, suggesting a regulatory function for these peptides on sweating. The present study evaluated the calcitonin-gene related peptide and substance P related regulation of sweating in man. Both calcitonin-gene related peptide and substance P, when administered alone, failed to cause sweat secretion, whereas sweating induced by methacholine chloride alone was four times greater when administered with calcitonin-gene related peptide and suppressed by 70% when administered with substance P. The degree of calcitonin-gene related peptide dependent augmentation and substance P dependent suppression of the methacholine chloride induced sweating was dependent on the concentration of calcitonin-gene related peptide and substance P. These findings suggest that calcitonin-gene related peptide enhances cholinergic sweating and substance P inhibits it.

Adult↗

PubMed1996

Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus.

OBJECTIVES: This study sought to determine whether nitric oxide-mediated vasodilation is abnormal in patients with non-insulin-dependent diabetes mellitus. BACKGROUND: Multiple investigations, both in experimental models and in patients with insulin-dependent diabetes mellitus, demonstrate impaired endothelium-dependent vasodilation. Decreased availability of endothelium-derived nitric oxide may contribute to the high prevalence of vascular disease in diabetes. METHODS: Vascular reactivity was measured in the forearm resistance vessels of 21 patients with non-insulin-dependent diabetes mellitus and 23 matched healthy control subjects. No patient had hypertension or hypercholesterolemia. Each subject was pretreated with aspirin to inhibit endogenous production of vasoactive prostanoids. Methacholine chloride (0.3 to 10 microg/min) was administered through a brachial artery cannula to assess vasodilation to endothelium-derived nitric oxide. Sodium nitroprusside (0.3 to 10 microg/min) was infused to evaluate vasodilation to an exogenous nitric oxide donor. Verapamil (10 to 300 microg/min) was administered to distinguish impaired nitric-oxide-mediated vasodilation from general dysfunction of vascular smooth muscle. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each agent. To assess the role of vasoconstrictor prostanoids, a subset of eight diabetic subjects were reexamined in the absence of aspirin treatment. RESULTS: Basal forearm blood flow in diabetic and nondiabetic subjects was comparable. The forearm blood flow responses to both methacholine chloride and nitroprusside were significantly attenuated in diabetic compared with nondiabetic subjects (p < 0.005 by analysis of variance for both agents). In contrast, the response to verapamil was not significantly different between the groups (p > 0.50). The forearm blood flow responses to these agents were not significantly affected by cyclooxygenase inhibition. CONCLUSIONS: Nitric oxide-mediated vasodilation is impaired in non-insulin-dependent diabetes mellitus. Vasoconstrictor prostanoids do not contribute significantly to vascular dysfunction. The attenuated response to exogenous as well as endogenous nitric oxide donors suggests that the abnormality is due to increased inactivation of nitric oxide or to decreased reactivity of the vascular smooth muscle to nitric oxide.

Adult↗

PubMed1986

Methacholine sensitivity and cAMP protein kinase in tracheal smooth muscle.

We studied regional variation in canine trachealis smooth muscle sensitivity and responsiveness to methacholine as well as basal and methacholine-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-dependent protein kinase activity. The trachea between the cricoid cartilage and the carina was divided into three segments of equal length (designated cervical, middle, and thoracic regions), each consisting of approximately 12-14 cartilage rings. Smooth muscle strips from each of the three regions were exposed to cumulative half-log increments of methacholine chloride. The sensitivity (-log EC50) and responsiveness (force per cross-sectional area and force per milligram protein) of the smooth muscle to methacholine in each region was determined from these data. Smooth muscle strips from cervical and thoracic regions were frozen before and after exposure to cumulative half-log increments of methacholine up to each region's previously determined EC50. Frozen samples were assayed for cAMP content or cAMP-dependent protein kinase activity. The relationship between resting tension and methacholine sensitivity and responsiveness were studied. For the size strips we used, 4 g resting tension set the average cervical and thoracic strips at 96 and 101% of their optimal length, respectively. The methacholine EC50 was not affected by a variation in resting tension. Sensitivity to methacholine was 7.1, 6.8, and 6.5 for cervical, middle, and thoracic regions, respectively. The responsiveness of the cervical and thoracic smooth muscle to methacholine was 16.4 and 16.3 g force/mm2, respectively, at an EC50 methacholine. Basal cAMP was lower in cervical smooth muscle than in thoracic. cAMP-dependent protein kinase activity ratios under both basal and EC50 methacholine-stimulated conditions were lower in cervical smooth muscle than in thoracic. We have observed in trachealis smooth muscle an inverse relationship between methacholine sensitivity and either cAMP or cAMP-dependent protein kinase activity. We suggest that cAMP and cAMP-dependent protein kinase play a role in the regulation of airway smooth muscle sensitivity to cholinergic agonists.

Animals↗

PubMed1984

Airway responses in offspring of dogs with and without airway hyperreactivity.

We examined airway responsiveness to aerosols of Ascaris suum, citric acid, and methacholine chloride in the offspring of two highly allergic breeds of dogs: Basenji-greyhounds (BG) and Basenjis (B). The BG parents had airway hyperresponsiveness to citric acid and methacholine, whereas the B parents did not. Both BG and B offspring were allergic as measured by many positive skin tests. BG offspring, like their parents, were hyperresponsive to citric acid and methacholine, whereas B offspring were not. We conclude that familial rather than environmental factors are important for the development of nonspecific airway hyperresponsiveness as well as allergy in the BG dog model of asthma. Allergic asthma in these animals represents a combination of two discrete processes: allergy and nonspecific airway hyperresponsiveness.

Airway Resistance↗

PubMed2005

Indinavir impairs endothelial function in healthy HIV-negative men.

BACKGROUND: Potent antiretroviral treatment has drastically reduced mortality in HIV-infected patients but may accelerate atherosclerotic disease, which could be partially mediated via endothelial dysfunction. METHODS: In 8 HIV-negative healthy males, leg blood flow responses to intraartery infusions of methacholine chloride (Mch), sodium nitroprusside, and NG-mono-methyl-L-arginine (L-NMMA) were measured before and after 4 weeks of daily oral indinavir. In the same subjects, we also assessed the effect of indinavir on lipids, insulin sensitivity, markers of inflammation, as well as oxidative stress. RESULTS: After 4 weeks of indinavir, the endothelium-dependent response to methacholine chloride was impaired (195% +/- 38% vs 83% +/- 13%, P < .05), the response to NG-mono-methyl-L-arginine (nitric oxide-dependent tone) was nearly abrogated (-30% +/- 4% vs -1% +/- 11%, P < .05), whereas the endothelium-independent response to sodium nitroprusside remained unchanged. Fasting insulin levels increased from 5.8 +/- 1.2 to 7.0 +/- 1.4 microU/mL (P < .05), and HOMA-IR scores increased from 1.3 +/- 0.3 to 1.6 +/- 0.3 U (P < .05). There were no changes in blood pressure, lipids, markers of inflammation, or oxidative stress. CONCLUSIONS: Four weeks of the HIV-1 protease inhibitor indinavir, in the absence of HIV-1 infection, causes vascular dysfunction most likely at the level of endothelial nitric oxide production. The vascular dysfunction may be mediated partially by the concomitant induction of insulin resistance but other mechanisms cannot be ruled out.

Adult↗

PubMed1984

Interaction between histamine and vagal stimulation on tracheal smooth muscle in dogs.

We examined the interaction between histamine and vagal efferent activity on airway smooth muscle reactivity in 11 anesthetized vagotomized dogs using an isolated closed segment of the intrathoracic trachea filled with Tyrode solution under an isovolumetric condition. Intratracheal pressure change was measured as an index of tracheal smooth muscle tone. The administration into the tracheal segment of histamine (0.1 or 1.0 mg/ml) in six dogs and methacholine chloride (0.001 or 0.01 mg/ml) in the other five dogs elevated intratracheal pressure by about 5 cmH2O. The electrical stimulation of the peripheral ends of both of the cut cervical vagus nerves in the presence of histamine produced significantly greater responses than the additive responses of these two stimuli applied individually (two-way analysis of variance, P less than 0.025). However, the combined effects of vagal stimulation and methacholine were not significantly different from the additive responses of these two stimuli applied individually. The average values of intratracheal pressure elevated by the combined effects of vagal stimulation and histamine were significantly higher than those obtained by the combination of vagal stimulation and methacholine (two-way analysis of variance, P less than 0.01). This suggests that histamine potentiates tracheal smooth muscle reactivity to electrical vagal stimulation, which may contribute to the hyperreactivity observed in patients with asthma.

Animals↗

PubMed1982

Medical therapy for experimental hypotony.

Experimental hypotony was induced in rhesus monkeys by the following procedures: ciliochoroidal detachment, retinal detachment, or cyclodialysis. Two days later, at the time of greatest hypotony, 10% methacholine chloride was deposited in the cornea by iontophoresis, and 0.25% physostigmine salicylate ointment was applied topically to each eye. The intraocular pressure rose to normal levels in all eyes for eight to 24 hours. The peak rise in IOP occurred one to four hours after drug administration and was 7.2, 6.8, and 11.3 mm Hg higher than the pretreatment levels in eyes with ciliochoroidal detachment, retinal detachment, and cyclodialysis, respectively. In a group of normal eyes, this drug combination caused a transient 5.7 mm Hg fall in IOP. The mechanism of pressure elevation by methacholine and physostigmine probably is caused by stimulation of aqueous humor formation or reduced uveoscleral outflow, or both.

Administration, Topical↗

PubMed1981

Clinical applicability of a methacholine inhalational challenge.

Cough, dyspnea, and chest pain are symptoms common to many cardiopulmonary diseases. A comprehensive evaluation, including a history, physical examination, ECG, chest roentgenogram, and pulmonary function studies, will often yield a specific diagnosis. However, when these symptoms are intermittent, as they often are in patients with bronchial asthma, the diagnosis may not be apparent. If asthma is thought to be a diagnostic possibility, a bronchial inhalation challenge should be used to demonstrate bronchial hyperreactivity, the hallmark of asthma. The methacholine chloride inhalation challenge is a simple and useful laboratory test to diagnose bronchial hyperreactivity. We describe eight patients with a variety of clinical symptoms to demonstrate the usefulness of this test. Patients with unexplained respiratory symptoms should be considered for bronchial inhalation challenge before proceeding to more invasive diagnostic procedures.

Adult↗

PubMed1989

Assessing clamp-related vascular injuries by measurement of associated vascular dysfunction.

The development of vascular clamps requires a reliable method to quantitate clamp-related vascular injuries. The degree of vessel damage usually is estimated subjectively from photomicrographs made with scanning electron microscopy. In order to test whether the use of vascular rings to assess residual vascular function may be a better method, rabbit thoracic aortas were occluded by five types of clamps: a Fogarty softjaw bulldog, a Fogarty Hydragrip, a 6-inch Satinsky clamp, an Edslab bulldog, and a silicone vessel band. Each area of clamp injury was sectioned into a vascular ring and suspended in a tissue bath. Residual vascular function was determined by contraction in response to phenylephrine and by relaxation in response to methacholine chloride and sodium nitroprusside. Morphologic studies with use of Evans blue dye and scanning electron microscopy complemented the vascular-function studies. The Fogarty bulldog clamp was the best at preserving vascular contraction and relaxation; the more crushing Satinsky clamp was the worst. The testing of vascular rings for residual function appears to be a useful technique for objectively quantitating vascular clamp-related vascular damage.

Animals↗

PubMed1984

Relationship between regional ventilation and aerosol deposition in tidal breathing.

The regional distribution of the deposition of 1.2 micron particles of 99mTc sulfur colloid inhaled by tidal breathing was compared with the distribution of ventilation as measured by a 133Xe washout technique. Twelve subjects were studied, 6 with normal pulmonary function tests, 5 with air-flow limitation, and 1 with unilateral phrenic nerve paralysis. Both xenon and aerosol were inhaled at tidal volume by the subjects while seated upright. A large field gamma camera acquired posterior scans. Thirteen experiments were also done on 7 dogs: 1 with extrathoracic obstruction of the airway to 1 lung, and 12 with bronchoconstriction from the instillation of methacholine chloride into the airways of a lower lobe. Two of these dogs were studied with a gamma camera system, and the others were studied with a Picker multi-probe system. Both in humans and in dogs, an increase in time constant, which indicated a decrease in ventilation, was associated with an increase in peripheral aerosol deposition when normalized for ventilation. It is suggested that the increased residence time is responsible for the increased deposition in regions that received lesser ventilation.

Adult↗

PubMed1986

Methacholine-induced airway reactivity of inbred rats.

Dose-response curves to inhaled aerosolized methacholine chloride (MCh) were obtained in anesthetized spontaneously breathing rats. Thirty rats (10/strain), randomly selected from highly inbred ACI, Lewis (L), and Brown Norway (BN) strains and 40 rats (20/strain) from similarly inbred Wistar-Furth (WF) and Buffalo (Buf) strains were studied. Airway responses were quantitated from changes in pulmonary resistance (RL) and airway reactivity was calculated as the dose of MCh required to increase RL to 150% (ED150RL) and 200% (ED200RL) of base line. There were no statistically significant differences in ED150RL and ED200RL among the five rat strains. Large interindividual variability was present as evidenced by 128-fold differences in ED150RL and ED200RL between the least and most sensitive animal of the same strain. In contrast, seven animals studied repeatedly on different days had values of ED150RL that differed by an average of only 2.9-fold (range 1.6-5.3). Thirteen rats that were studied on two occasions separated by an interval of 3 mo showed no systematic changes in airway reactivity. We conclude that airway reactivity to inhaled methacholine in anesthetized nose-breathing rats is not strain related, and despite animals of a given strain being genetically identical, the variability in airway reactivity within strains suggests that environmental rather than genetic factors are the major determinants of that reactivity.

Airway Resistance↗

PubMed1987

Local effect of vasoactive intestinal polypeptide on human sweat-gland function.

Physiological significance of vasoactive intestinal polypeptide (VIP), a putative co-transmitter of the cholinergic neuron innervating sweat glands, was investigated by its local effect on drug-induced sweating. VIP, methacholine chloride (MCH), or VIP plus MCH dissolved in 0.1 ml of 0.9% NaCl solution to a specified concentration was injected intradermally at the center of a forearm test area of 15 cm2 and the sweat rate was recorded continuously by capacitance hygrometry. In a cool environment (Ta, 23 degrees C), VIP failed to cause sweat secretion, but increased the rate of MCH-induced sweating, most markedly at a concentration of 10(-5) g/ml, where the rise in local skin temperature was the greatest. On an area anesthetized by nerve block in a hot environment (Ta, 35 degrees C), the effect was less obvious and less consistent, indicating that the sweat-facilitatory effect of VIP is reduced under the condition of passive cutaneous vasodilation. It may be postulated that VIP plays a role in securing ample oxygen supply to functioning sweat glands, especially with a relatively high cutaneous vasoconstrictor tone.

Adult↗

PubMed1984

Bronchial responsiveness to methacholine and effects of respiratory maneuvers.

Eight asthmatic and six normal subjects had methacholine chloride inhalation tests on two visits. On first assessment the provocative concentration causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) was measured. On the second visit the provocative concentration causing a 35% fall in specific lung conductance (PC35sGL) was obtained in addition to the PC20FEV1. Lung resistance was continuously monitored to evaluate the bronchomotor effect of FEV1 maneuver. Results of PC20FEV1 were within one single twofold concentration on the two visits. In all subjects but one PC35sGL was lower than PC20FEV1, and in 10 instances this difference was superior to a single twofold concentration. The bronchodilator effect of FEV1 maneuver was significantly although loosely related to base-line airway caliber and excitability. However, we were unable to show a significant relationship between the differences between PC20FEV1 and PC35sGL and this bronchodilator effect. This suggests that other factors may explain the greater sensitivity of PC35sGL compared with PC20FEV1.

Asthma↗

PubMed1984

Extracellular calcium ion depletion induces release of glycoproteins by canine trachea.

The effect of depletion of extracellular Ca2+ on the release by canine trachea in vitro of [14C]glucosamine-labeled trichloroacetic-phosphotungstic acid-precipitable glycoproteins was evaluated. Incubation in Ca2+,Mg2+-free medium containing ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA, 10(-3) to 10(-5) M) induced a time-dependent increase in base-line release of high molecular weight, radiolabeled glycoprotein that was not blocked by 10(-5) M atropine, propranolol, or phentolamine. Maximal increase was proportional to EGTA concentration and was augmented by preincubation with methacholine chloride. The secretory response was reversed by reincubation of explants in medium containing Ca2+, Sr2+, or Ba2+ but not Mg2+. Assessment of explants denuded of epithelium or cartilage indicated that the secretory response to depletion of Ca2+ originated in the tracheal submucosa, probably the submucosal glands. Quantitative autoradiographic analyses showed, however, that incubation in Ca2+,Mg2+-free medium had no effect on radiolabel release from mucous or serous cells in the tracheal submucosal glands. Increased radiolabeled glycoprotein release in Ca2+,Mg2+-free medium was accompanied by exfoliation of the surface epithelium, though the two effects were apparently unrelated. The secretory response was not due to cell lysis or increased release of radiolabeled glycosaminoglycans, and the finding that the specific activity (ratio of bound radiolabel to protein content) of the glycoprotein released was not changed in Ca2+,Mg2+-free medium showed that it was not due to a change in the rate of glycoprotein synthesis. A model is proposed in which depletion of Ca2+ increases the rate of flow of mucus from the duct lumens of the tracheal glands.

Animals↗

PubMed1984

Cyclic GMP accumulation during cholinergic stimulation of eccrine sweat glands.

The possibility that guanosine 3'5'-cyclic monophosphate (cGMP) may be an intracellular mediator of cholinergic stimulation [methacholine chloride (MCh)] was explored by comparing the relationship between the time course of cGMP accumulation and sweat secretion by use of isolated monkey palm eccrine sweat glands. Isolated sweat glands were incubated with MCh or other agents, and tissue levels of cGMP were determined by radioimmunoassay. In parallel experiments, sweat secretion was induced from cannulated single sweat glands in vitro. Stimulation with MCh produced a Ca-dependent transient elevation of cGMP level from 10 to 80 fmol/gland, peaking at 1-2 min but returning to the basal level by 5 min. The MCh-induced cGMP level was dose dependent and was inhibited by atropine. Ionophore A23187 (2 X 10(-4) M), however, caused persistent elevation of cGMP level for at least 20 min. Neither 10(-4) M MNNG, which elevated the cGMP level comparably with MCh stimulation, nor 8-bromo-cGMP (2 mM) induced sweat secretion. Thus although a parallelism between the cGMP level and sweating rate appears to hold for the initial stage of MCh-induced sweating, it does not hold for the steady state of sweat secretion. Data could not be interpreted to favor the notion that cGMP may be the intracellular mediator of cholinergic sweat secretion.

Animals↗