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Beta-blockers are currently contraindicated in asthma because their acute administration may be associated with worsening bronchospasm. However, their effects and safety with their chronic administration are not well evaluated. The rationale for this pilot study was based on the paradigm shift that was observed with the use of beta-blockers in congestive(More)
Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that(More)
We studied the repair of lung injury in adult rats exposed to 100% oxygen for 60 h, then placed in ambient air. Lung ornithine decarboxylase (ODC) activity and polyamine (putrescine, spermidine, and spermine) content during repair were correlated with changes in lung ultrastructure. The effect of difluoromethylornithine (DFMO), a selective Irreversible ODC(More)
BACKGROUND We have previously reported that chronic treatment with certain 'beta-blockers' reduces airway hyperresponsiveness (AHR) to methacholine in a murine model of asthma. METHODS Airway resistance was measured using the forced oscillation technique in ovalbulmin-sensitized and ovalbulmin-challenged mice treated with several beta-adrenoceptor(More)
beta(2)-adrenoceptor agonists are the mainstay for the acute symptomatic treatment of asthma and provide effective bronchoprotection to a wide range of bronchoconstrictor agents. However, over the past 4 decades there has been a continuing debate concerning whether regular chronic treatment with these drugs may be doing more harm than good. The FDA's recent(More)
We studied changes in lung ultrastructure and collagen content during the repair of acute lung injury in adult rats exposed to 100% O2 for 60 h and recovering in ambient air. In the interstitium, during the first 3 days of repair, the number of neutrophils decreased 16-fold, and monocytes and lymphocytes increased to 7-fold and 4-fold the respective control(More)
Chronic regular use of beta(2)-adrenoceptor (beta(2)-AR) agonists in asthma is associated with a loss of disease control and increased risk of death. Conversely, we have found that administration of beta(2)-AR inverse agonists results in attenuation of the asthma phenotype in an allergen-driven murine model. Besides antagonizing agonist-induced signaling(More)
Inverse agonism has gone from an initial curiosity to a now well-recognized phenomenon. This has demanded expansion of receptor theory models to account for multiple receptor states and a re-definition of ligand efficacy. However, after several decades of discovery, the clinical importance of inverse agonist ligands is still speculative because this work is(More)
These studies show that very soon after exposure of canine lungs to crude papain mixed with a marker (India ink), the alveolar surface-active lining was both morphologically and functionally altered, and alveolar macrophages were destroyed in significant numbers. These changes occurred before other identifiable major alterations. The morphologic changes(More)
BACKGROUND AND PURPOSE Our previous studies have shown the β2 -adrenoceptor and its endogenous ligand, adrenaline, are required for development of the asthma phenotype in murine asthma models. Chronic administration of some, but not other, β-blockers attenuated the asthma phenotype and led us to hypothesize that biased signalling was the basis of their(More)