Hyperresponsiveness In Rats Research Articles

The regulation of IL-12: Its role in infectious, autoimmune, and allergic diseases

The regulation of IL-12: Its role in infectious, autoimmune, and allergic diseases

P-624 - Pharmacological studies on the respiratory tract (Rept. 212) : Alteration of protein kinase C (PKC) levels at the antigen-induced airway hyper-responsiveness in rats

P-624 - Pharmacological studies on the respiratory tract (Rept. 212) : Alteration of protein kinase C (PKC) levels at the antigen-induced airway hyper-responsiveness in rats

P-532 - Pharmacological studies on the respiratory tract (Rept. 207): Gq protein level increases at the antigen-induced airway hyperresponsiveness in rats

P-532 - Pharmacological studies on the respiratory tract (Rept. 207): Gq protein level increases at the antigen-induced airway hyperresponsiveness in rats

Attenuation of Airway Hyperresponsiveness During Acute Viral Infection Using the 21-Aminosteroid U-83836E in Rats

Respiratory viral infections have been associated with exacerbations of asthma in humans, and are known to produce airway obstruction and hyperresponsiveness in rats. Virus-induced airway dysfunction may result in part from inflammatory cells and their products, and agents that target these mechanisms might therefore attenuate viral airway injury. The 21-aminosteroid class of drugs has been reported to attenuate tissue injury in a variety of models, and we hypothesized that U-83836E, an orally-active aminosteroid, would prevent the development of airway dysfunction during acute viral illness. Adult rats were inoculated with either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated rats were placed in a body plethysmograph for measurements of airway obstruction (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to iv methacholine; lungs were lavaged to obtain inflammatory cells. The water–treated virus group was significantly different from the non-infected controls for all variables. Virus-induced hyperresponsiveness was attenuated (P=0.027) by aminosteroid treatment, although airway obstruction and inflammation were not improved by the treatment. We conclude that 21-aminosteroids may protect airways from virus-induced hyperresponsiveness.

Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization.

The efficacy of an "allergen-gene immunization" protocol in altering allergic response was examined. Intramuscular injection of rats with a plasmid DNA encoding a house dust mite allergen into the muscle results in its long-term expression and the induction of specific immune responses. Significantly, this approach prevents the induction of immunoglobulin E synthesis, histamine release in bronchoalveolar fluids, and airway hyperresponsiveness in rats challenged with aerosolized allergen. Furthermore, this suppression is persistent and can be transferred into naive rats by CD8+ T cells from gene-immunized rats. These findings suggest that allergen-gene immunization is effective in modulating allergic responses, and may provide a novel therapeutic approach for allergic diseases.

P-565 - Pharmacological studies on the respiratory tract (Rept. 200): Elevated nitric oxide synthase activity at antigen-induced airway hyperresponsiveness in rats.

P-565 - Pharmacological studies on the respiratory tract (Rept. 200): Elevated nitric oxide synthase activity at antigen-induced airway hyperresponsiveness in rats.

Characteristics of muscarinic cholinoceptors in airways of antigen-induced airway hyperresponsive rats

The antagonist and agonist binding sites of muscarinic receptors were investigated by using membrane preparations of airways from nonsensitized normal control, sensitized control and repeatedly antigen challenged rats. The in vitro bronchial responsiveness to ACh was markedly increased in repeatedly antigen challenged group but not in sensitized control group. No significant difference was observed in receptor density and antagonist affinity among these three groups. The affinity of ACh for high-affinity agonist binding sites of repeatedly antigen challenged group was much greater than those in the other groups; the affinity significantly reduced in the presence of GTPγS. We concluded that enhanced G protein level might be involved in inducing airway hyperresponsiveness in rats.

Urban Levels of Air Pollution Increase Lung Responsiveness in Rats

This study was designed to investigate if animals exposed to urban levels of air pollution develop pulmonary hyperresponsiveness and to test if this change was reversed after moving the animals to a nonpolluted environment. One hundred twenty male Wistar rats were kept in (a) São Paulo (polluted environment) for 3 months (SP3); (b) Atibaia (clean region), for 3 months (A3); (c) São Paulo for 3 months and then Atibaia for a further 3 months (SPA6); (d) Atibaia for 6 months (A6). After the exposure period, the rats were submitted to dose-response curves to inhaled methacholine. Older animals (SPA6 and A6) had lower responses to methacholine in terms of respiratory system resistance when compared to the animals studied after 3 months of experiment (SP3 and A3). However, the response in terms of respiratory system elastance of the SP3 group was significantly (P = 0.0004) greater than those of the other three groups. Our results suggest that the environmental conditions of the large urban centers can induce pulmonary hyperresponsiveness in rats that can be reversed when the animals are removed to a nonpolluted area.

Alteration in Ca 2+ availability involved in antigen-induced airway hyperresponsiveness in rats

The origin of Ca 2+ contributing to the enhancement of acetylcholine-induced bronchial smooth muscle constriction in airway hyperresponsiveness induced by antigen challenge was investigated. Under Ca 2+-free (concomitant with 10 −6 M nicardipine) conditions, the contractile responses of bronchial rings to 1 mM acetylcholine were significantly greater in rings from rats with hyperresponsive airways (0.15 ± 0.04 g) than those of rings from normal rats (0.02 ± 0.004 g; P < 0.05). The cumulatively administered Ca 2+ induced a markedly greater bronchoconstriction in rings from rats with hyperresponsive airways in Ca 2+-free solution when muscles were pretreated with 1 mM acetylcholine (in the presence of 10 −6 M nicardipine) than in rings from normal rats, whereas no significant difference in Ca 2+-induced bronchoconstriction was observed between the two groups when muscles were pretreated with 60 mM K + (in the presence of 10 −6 M atropine). These findings suggest that enhancement of the availability of Ca 2+ released from intracellular stores and/or influxed through receptor-operated Ca 2+ channels in airway smooth muscles might be involved in the airway hyperresponsiveness to acetylcholine in rats.

Gonadectomy does not prevent novelty or drug-induced motor hyperresponsiveness in rats with neonatal hippocampal damage

To explore the possibility that gonadal hormones are required for triggering the postpubertal emergence of enhanced dopamine-related behaviors in rats with neonatal excitotoxic lesions of the ventral hippocampus (VH), we assessed behavioral changes in castrated VH lesioned rats. The VH of rat pups was lesioned with ibotenic acid on day 7 after birth (PD7). Rats were castrated on PD21. Novelty- and amphetamine-induced locomotor activity were tested on PD56, and apomorphine-induced stereotypic behaviors and locomotion were evaluated on PD98. As demonstrated previously, the VH lesioned rats expressed enhanced novelty-, amphetamine- and apomorphine-induced hyperlocomotion (PD56) as well as potentiated apomorphine-induced stereotypic behaviors (PD98) in young adulthood as compared with sham-lesioned counterparts. Castration had no significant effect on novelty-induced locomotion or apomorphine-induced stereotypies but potentiated amphetamine- and apomorphine-induced hyperactivity in lesioned rats. These results indicate that the absence of gonadal hormones not only does not prevent the appearance in adulthood of behavioral disturbances linked to increased DA transmission in rats with neonatal lesions of the VH but even exaggerates those linked primarily to the mesolimbic DA system.

P-251 - Pharmacological studies on the respiratory tract (Rept 187): Modulation of cholinergic neuro transmission by opioids in airway hyperresponsiveness in rats.

P-251 - Pharmacological studies on the respiratory tract (Rept 187): Modulation of cholinergic neuro transmission by opioids in airway hyperresponsiveness in rats.

O-52 - Pharmacological studies on the respiratory tract (Rept. 171): Role of sensory neuropeptides in airway hyperresponsiveness in rats.

O-52 - Pharmacological studies on the respiratory tract (Rept. 171): Role of sensory neuropeptides in airway hyperresponsiveness in rats.

Tumor Necrosis Factor Causes Bronchial Hyperresponsiveness in Rats

We have previously reported that exposure of rats to aerosolized endotoxin (LPS) causes a transient, dose-dependent increase in bronchial responsiveness (BR) to 5 hydroxytryptamine (5HT), 90 min after exposure. In the present study we examined whether LPS induces the release of tumor necrosis factor (TNF) in the airways and whether TNF contributes to the increase in BR. After 90 min following exposure to aerosolized LPS, at a concentration of 1 or 10 micrograms/ml, TNF concentrations in bronchoalveolar lavage (BAL) fluid were 17.9 +/- 6.9 and 80.5 +/- 7.8 U/ml, respectively. No TNF was detected in BAL fluid of saline-exposed animals. At 90 min after exposure to aerosolized recombinant human TNF (rhTNF) (1 microgram/ml) an increase in BR was observed: the provocative concentration of 5HT causing a 50% increase in lung resistance (PC50RL 5HT) was 2.7 +/- 0.4 versus 4.4 +/- 0.3 microgram/kg in saline-exposed animals (p less than 0.01). Pretreatment with anti-TNF antibodies 30 min before LPS exposure significantly diminished the increase in BR: PC50RL 5HT was 2.3 +/- 0.4 versus 1.2 +/- 0.5 microgram/kg in control pretreated LPS-exposed rats (p less than 0.01). Exposure to aerosolized TNF also induced a significant influx of neutrophils in BAL fluid (12.1 +/- 3.7 versus 1.7 +/- 0.4% in saline-exposed animals) (p less than 0.01). The LPS-induced neutrophil influx in BAL fluid was partly inhibited by pretreatment with anti-TNF antibodies (55.2 +/- 5.1 versus 76.0 +/- 3.9%) (p less than 0.01). We conclude that TNF causes bronchial hyperresponsiveness and airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Theophylline on Endotoxin and Tumor Necrosis Factor Induced Airway Changes in an in vivo Animal Model.

We have previously reported that exposure to aerosolized endotoxin causes bronchial hyperresponsiveness in rats. This is at least partly due to secondary release of tumor necrosis factor (TNF). In this study, we evaluated the effect of pretreatment with aminophylline on these lipopolysaccharide-induced airway changes. Compared to placebo-pretreated animals aminophylline (20 mg/kg i.p.) significantly inhibited the lipopolysaccharide-induced increase in responsiveness without influencing neutrophil counts or TNF levels in bronchoalveolar lavage fluid. In a second part of the study, aminophylline- or placebo-pretreated rats were exposed to aerosolized recombinant human TNF. Compared to saline-exposed animals, TNF caused a significant increase in 5-hydroxytryptamine responsiveness which was inhibited by pretreatment with aminophylline. We conclude that the attenuating effect of aminophylline on lipopolysaccharide-induced airway hyperresponsiveness is not due to inhibition of TNF release, but could be explained by its inhibitory effect on TNF-induced hyperresponsiveness.

Oral induction of the insulin hyper-responsiveness in rats with ventromedial hypothalamic lesions.

Bilateral electrolytic or sham-lesions of the ventromedial nuclei of the hypothalamus (VMH) were performed on fasting (prior to and after the lesion) ether anesthetized rats. Post-operatively (2 hours), sham-operated rats were either offered an oral glucose solution or were submitted to an intravenous glucose injection or were left undisturbed; lesioned rats were offered an oral glucose load or were submitted to an intravenous glucose injection. Three hours later, the insulin response to an intravenous glucose load was tested in all rats. No significant difference could be detected between the results obtained in the three subgroups of sham-operated rats. By contrast, the VMH lesioned rats exhibited a differential response according to the post-lesion treatment. In lesioned rats, given an intravenous glucose injection in the immediate post-lesion period, the tested insulin response was not significantly different from the response of the controls. When lesioned animals were allowed to taste and ingest as little at 0.5 g glucose, the tested insulin response was greatly enhanced. It is concluded that an oral intake is a prerequisite to the induction of the insulin hyper-responsiveness characteristic of fed VMH lesioned rats and that a 0.5 glucose oral intake is sufficient.