ovalbumin and Bradycardia

Although anticholinergic therapy inhibits bronchoconstriction in asthmatic patients and antigen-challenged animals, administration of atropine 1 h before antigen challenge significantly potentiates airway hyperreactivity and eosinophil activation measured 24 h later. This potentiation in airway hyperreactivity is related to increased eosinophil activation and is mediated at the level of the airway nerves. Since eosinophils produce nerve growth factor (NGF), which is known to play a role in antigen-induced airway hyperreactivity, we tested whether NGF mediates atropine-enhanced, antigen challenge-induced hyperreactivity. Antibody to NGF (Ab NGF) was administered to sensitized guinea pigs with and without atropine pretreatment (1 mg/kg iv) 1 h before challenge. At 24 h after challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated. Electrical stimulation of both vagus nerves caused bronchoconstriction that was increased in challenged animals. Atropine pretreatment potentiated antigen challenge-induced hyperreactivity. Ab NGF did not affect eosinophils or inflammatory cells in any group, nor did it prevent hyperreactivity in challenged animals that were not pretreated with atropine. However, Ab NGF did prevent atropine-enhanced, antigen challenge-induced hyperreactivity and eosinophil activation (assessed by immunohistochemistry). This effect was specific to NGF, since animals given control IgG remained hyperreactive. These data suggest that anticholinergic therapy amplifies eosinophil interactions with airway nerves via NGF. Therefore, therapeutic strategies that target both eosinophil activation and NGF-mediated inflammatory processes in allergic asthma are likely to be beneficial.

Topics: Animals; Antigens; Asthma; Atropine; Blood Pressure; Bradycardia; Bronchial Hyperreactivity; Bronchoconstriction; Bronchodilator Agents; Electric Stimulation; Eosinophils; Female; Guinea Pigs; Heart Rate; Muscle, Smooth; Nerve Growth Factor; Ovalbumin; Parasympathetic Nervous System; Receptor, Muscarinic M2; Specific Pathogen-Free Organisms; Vagotomy; Vagus Nerve

Recent epidemiologic studies have identified organophosphorus pesticides (OPs) as environmental factors potentially contributing to the increase in asthma prevalence over the last 25 years. In support of this hypothesis, we have demonstrated that environmentally relevant concentrations of OPs induce airway hyperreactivity in guinea pigs.. Sensitization to allergen is a significant contributing factor in asthma, and we have shown that sensitization changes virus-induced airway hyperreactivity from an eosinophil-independent mechanism to one mediated by eosinophils. Here, we determine whether sensitization similarly influences OP-induced airway hyperreactivity.. Nonsensitized and ovalbumin-sensitized guinea pigs were injected subcutaneously with the OP parathion (0.001-1.0 mg/kg). Twenty-four hours later, animals were anesthetized and ventilated, and bronchoconstriction was measured in response to either vagal stimulation or intravenous acetylcholine. Inflammatory cells and acetylcholinesterase activity were assessed in tissues collected immediately after physiologic measurements.. Ovalbumin sensitization decreased the threshold dose for parathion-induced airway hyperreactivity and exacerbated parathion effects on vagally induced bronchoconstriction. Pretreatment with antibody to interleukin (IL)-5 prevented parathion-induced hyperreactivity in sensitized but not in nonsensitized guinea pigs. Parathion did not increase the number of eosinophils in airways or the number of eosinophils associated with airway nerves nor did it alter eosinophil activation as assessed by major basic protein deposition.. Antigen sensitization increases vulnerability to parathion-induced airway hyperreactivity and changes the mechanism to one that is dependent on IL-5. Because sensitization to allergens is characteristic of 50% of the general population and 80% of asthmatics (including children), these findings have significant implications for OP risk assessment, intervention, and treatment strategies.

Topics: Acetylcholinesterase; Animals; Bradycardia; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Dose-Response Relationship, Drug; Electric Stimulation; Female; Guinea Pigs; Immunization; Interleukin-5; Ovalbumin; Parathion; Pesticides; Vagus Nerve

Topics: Anaphylaxis; Animals; Blood Pressure; Bradycardia; Femoral Artery; Heart Rate; Heart Ventricles; Hemodynamics; Hypotension; Ovalbumin; Rats

Topics: Action Potentials; Anaphylaxis; Animals; Antibodies; Antigen-Antibody Reactions; Arrhythmias, Cardiac; Bradycardia; Cardiac Complexes, Premature; Electrocardiography; Gastric Mucosa; Guinea Pigs; Heart; Heart Block; Heart Rate; Hypersensitivity, Delayed; In Vitro Techniques; Injections, Intravenous; Intestine, Small; Ischemia; Myocardium; Ovalbumin; Tachycardia; Wolff-Parkinson-White Syndrome