Enhancement of airway reactivity to histamine by isoprenaline and related β‐adrenoceptor agonists in the guinea‐pig

Galland, Barbara; Blackman, J. G.

doi:10.1111/j.1476-5381.1993.tb13499.x

Cited by 26 publications

(10 citation statements)

References 20 publications

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“…Although the mechanisms are not yet clear, i.v. infusion of isoproterenol has been shown to increase airway reactivity in guinea pigs (15,16) and to produce rebound bronchospasm in some asthmatic patients (17). In our study, NKH477, like forskolin (18), did not enhance the bronchoconstriction induced by histamine after the infusion, in contrast to isoproterenol.…”

Section: Statistical Analysescontrasting

confidence: 39%

Bronchodilator and Cardiovascular Effects of NKH477, a Novel Water-Soluble Forskolin Derivative, in Guinea Pigs

Iida

Fujita

Hosono

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-The bronchodilator and cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride) were evaluated. In anesthetized guinea pigs, i.v. bolus injections of NKH477 (1-100 pg/kg) inhibited the bronchoconstriction induced by inhaled leukotriene D4, increased the heart rate (HR) and decreased the diastolic arterial blood pressure (DBP) in a dose-dependent manner. The bronchodilator effect of NKH477 was 1500 times more potent than that of aminophylline and 17 times less potent than that of isoproterenol. The selectivity of NKH477 for bronchodilation vs an increase in HR was 15 times higher than that of isoproterenol and similar to that of aminophylline; and vs a decrease in DBP, the selectivity was 4 times higher than that of aminophylline and similar to that of isoproterenol. I.v. infusion of NKH477 (0.1-3 fig/kg/min) for 2 hr dose-dependently inhibited the bronchoconstriction induced by i.v. histamine. Isoproterenol (0.1 1,,g/kg/min, i.v.) enhanced the bronchoconstriction after termination of the infusion, whereas NKH477 did not. In conscious guinea pigs, inhalation of NKH477 (0.1-5 mg/ml) concentrationdependently inhibited the bronchoconstriction induced by inhaled histamine, and a high concentration of NKH477 (35.4 mg/ml) increased the HR. The bronchodilator effect of inhaled NKH477 was 15 times less potent than that of isoproterenol. The selectivity of inhaled NKH477 was similar to that of isoproterenol. These results indicate that NKH477 may be useful as a bronchodilator.

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Section: Statistical Analysescontrasting

confidence: 39%

Bronchodilator and Cardiovascular Effects of NKH477, a Novel Water-Soluble Forskolin Derivative, in Guinea Pigs

Iida

Fujita

Hosono

et al. 1995

Japanese Journal of Pharmacology

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“…Although detailed medication intake of the donors in the last weeks of life is difficult to get, it is possible that end-of-life drugs or asthma medication, particularly long-acting b-agonists, may have reduced contractility. However, it is unlikely that pharmaceutical agents remain in effective concentrations after dissection and equilibration protocols, and prolonged exposure to b-agonists has been shown to lead to aggravated AHR (20,21).…”

Section: Discussionmentioning

confidence: 99%

Human Trachealis and Main Bronchi Smooth Muscle Are Normoresponsive in Asthma

Ijpma

Kachmar

Matusovsky

et al. 2015

Am J Respir Crit Care Med

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Rationale: Airway smooth muscle (ASM) plays a key role in airway hyperresponsiveness (AHR) but it is unclear whether its contractility is intrinsically changed in asthma.Objectives: To investigate whether key parameters of ASM contractility are altered in subjects with asthma.Methods: Human trachea and main bronchi were dissected free of epithelium and connective tissues and suspended in a force-length measurement set-up. After equilibration each tissue underwent a series of protocols to assess its methacholine dose-response relationship, shortening velocity, and response to length oscillations equivalent to tidal breathing and deep inspirations.Measurements and Main Results: Main bronchi and tracheal ASM were significantly hyposensitive in subjects with asthma compared with control subjects. Trachea and main bronchi did not show significant differences in reactivity to methacholine and unloaded tissue shortening velocity (Vmax) compared with control subjects. There were no significant differences in responses to deep inspiration, with or without superimposed tidal breathing oscillations. No significant correlations were found between age, body mass index, or sex and sensitivity, reactivity, or Vmax.Conclusions: Our data show that, in contrast to some animal models of AHR, human tracheal and main bronchial smooth muscle contractility is not increased in asthma. Specifically, our results indicate that it is highly unlikely that ASM half-maximum effective concentration (EC 50 ) or Vmax contribute to AHR in asthma, but, because of high variability, we cannot conclude whether or not asthmatic ASM is hyperreactive.

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“…Although (S)-albuterol does not function as a β 2 -agonist, it has been shown to exert biological effects on airway smooth muscle and inflammatory cells. (S)-Albuterol induces paradoxical reactions in airways and may decrease asthma control, although the mechanism whereby (S)-albuterol evokes hyperresponsiveness appears to be unrelated to β 2 -adrenoceptor activation [6, 9]. Furthermore, the metabolic clearance rate for (S)-albuterol is tenfold slower than that for (R)-albuterol [10, 11], which may result in accumulation of (S)-albuterol and subsequent potential adverse effects in asthma control.…”

Section: Introductionmentioning

confidence: 99%

(S)-Albuterol Increases the Production of Histamine and IL-4 in Mast Cells

Cho

Hartleroad

2001

Int Arch Allergy Immunol

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Background: Racemic albuterol is an equimolar mixture of (R)-albuterol and (S)-albuterol. Previous studies indicated that (S)-albuterol may exert proinflammatory effects. We investigated the effect of (S)-albuterol in the production of mast cell mediators such as histamine and interleukin (IL)-4. Methods: Murine mast cells were either unstimulated or stimulated by IgE-receptor crosslinking. Both groups of mast cells were pretreated with either (R)- or (S)-albuterol. Histamine release and IL-4 secretion were measured by ELISA. Expression of L-histidine decarboxylase (L-HDC) and IL-4 was analyzed by semiquantitative reverse transcription-polymerase chain re- action. Results: In the overnight IgE-stimulated group, secreted histamine and total histamine were approximately 19.9 and 18.3% greater in cells co-treated with (S)-albuterol than untreated cells, respectively (n = 4, p < 0.002, p < 0.02), whereas there was no significant difference between the cells treated with (R)-albuterol and untreated cells. When the IgE-stimulated cells were treated with (S)-albuterol for 6 and 24 h, histamine release was approximately 18.3 and 24% greater, respectively (n = 4, p < 0.01). L-HDC is an essential enzyme for synthesizing histamine and its message was significantly induced in mast cells treated with (S)-albuterol. Both IL-4 message and protein were also significantly increased after treatment with (S)-albuterol. In the overnight IgE-stimulated group, IL-4 secretion was increased by approximately 58.8% upon exposure to (S)-albuterol (n = 5, p < 0.01). (R)-albuterol had no effect on mast cell mediator release. Conclusion: (S)-albuterol may have adverse effects in asthma control by activating mast cells to produce inflammatory mediators such as histamine and IL-4.

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Enhancement of airway reactivity to histamine by isoprenaline and related β‐adrenoceptor agonists in the guinea‐pig

Cited by 26 publications

References 20 publications

Bronchodilator and Cardiovascular Effects of NKH477, a Novel Water-Soluble Forskolin Derivative, in Guinea Pigs

Bronchodilator and Cardiovascular Effects of NKH477, a Novel Water-Soluble Forskolin Derivative, in Guinea Pigs

Human Trachealis and Main Bronchi Smooth Muscle Are Normoresponsive in Asthma

(S)-Albuterol Increases the Production of Histamine and IL-4 in Mast Cells

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