Search

It has been shown that opioid peptides induce histamine release and enhance antigen-induced histamine release from isolated peritoneal mast cells. Little is known about the effect of opioid peptides on mast cells present in airway smooth muscle. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea pigs was studied. It appears that beta-endorphin has a bidirectional effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (0.1 and 10 nM) significantly potentiate the anaphylactic contractions of tracheal rings. In contrast, higher concentrations of beta-endorphin (0.1 and 1 microM) significantly suppress the anaphylactic contractions of guinea pig trachea. In the presence of the non-selective opioid receptor antagonist naloxone, 10 nM of beta-endorphin still potentiates the anaphylactic contractions of the trachea. This demonstrates that the potentiation of anaphylactic contractions of guinea pig trachea by low concentrations of beta-endorphin is not mediated by opioid receptors. We speculate that the potentiation of the anaphylactic contraction by beta-endorphin is due to an interaction with mast cells.

Guinea pigs were inoculated intra-tracheally with bovine parainfluenza type 3 virus (PI-3) to investigate airway responsiveness to histamine and arecoline in vitro. Two days after saline or PI-3 inoculation no difference in the reactivity of the tracheal spirals was observed after cumulative concentration/response curves with both drugs. Similarly, contractions of parenchymal strips, induced by histamine, did not differ between both groups. However, 4 days after PI-3 inoculation the histamine induced contraction of the tracheal spirals was increased by 47% and the arecoline induced contractions by 32% as compared to the control group. Further, the contractions induced by histamine in parenchymal strips were significantly enhanced (p less than 0.01) in the PI-3 treated group. In conclusion, PI-3 infection of guinea pig respiratory tract induces hyperreactivity of the central and peripheral airways in vitro.

In the present study we investigated the possible role of neutrophils and the endothelium in the induction of hyperreactivity of pig coronary arteries to histamine. Histamine caused a dose-dependent contraction of isolated pig coronary arteries. The maximal contraction to histamine was reduced in preparations from which the endothelium had been removed. Pre-incubation of intact coronary arteries with isolated neutrophils had no influence on the contractile response to histamine. However, when the same experiments were performed with coronary arteries without endothelium, the maximal contraction to histamine was increased. Incubation with scavengers and inhibitors of the enzymes, lipoxygenase or cyclo-oxygenase, provided evidence for a role of lipoxygenase products in the induction of hyperreactivity to histamine by neutrophils in the pig coronary artery.

The influence of the linoleic acid metabolite 13-hydroxy-octadecadienoic acid (13-HODE) on guinea pig tracheal reactivity to both contractile and relaxant agonists was investigated in vitro. 13-HODE induced an increased contraction of tracheal rings to histamine, whereas methacholine responsiveness was not significantly affected. Relaxant responses to isoprenaline and prostaglandin E2 were not influenced either.

Cultured epithelial cells obtained from guinea pig tracheal preparations metabolized arachidonic acid into 5- and 15-hydroxy-eicosatetraenoic acid and into the prostaglandins E2 and F2 alpha. Linoleic acid was converted by the epithelial cells into 9-hydroxy-octadecadienoic acid (9-HODE) and smaller amounts of 13-HODE. It was further investigated whether linoleic acid metabolites are of importance for the regulation of airway smooth muscle function. 13-HODE caused an increase of maximal contraction of tracheal rings to histamine, while 9-HODE had no effect.

In this study we investigated a possible relationship of delayed type hypersensitivity (DTH), as a model for cellular IgE-independent immunity, with the induction of airway hyperreactivity. In PC1 (picryl chloride) sensitized BALB/c mice DTH-like lung infiltrates were found that were maximal 48 hr after intranasal hapten challenge. During the elicitation of this DTH-like reaction tracheal hyperreactivity to the cholinergic agonist carbachol could be detected from 2 hr after challenge with the homologous hapten and that was maximal after 48 hr.

The effect of IL-2, IL-3, IL-4 and GM-CSF on beta-adrenoceptor function of human peripheral blood mononuclear cells (PBMC) was studied. After a 2 h pre-incubation period of PBMC with each of the lymphokines (1-100 units/ml), the isoprenaline stimulated cAMP production in these cells was not altered. However, IL-2 and GM-CSF induced a concentration dependent decrease of the beta-adrenoceptor agonist stimulated cAMP production after a 20 h pre-incubation period.

Migrating larvae of the canine nematode Toxocara canis induce inflammatory responses in the lungs of infected mice. Histological examination of the lungs showed that mice, developed persistent multifocal inflammation in which eosinophils (eos), macrophages (M phi) and many lymphocytes were involved. Cuffing of blood vessels and bronchioles with mixed cell populations was also observed. Investigation into the response of isolated tracheae to cholinergic and beta-adrenergic receptor agonists demonstrated a significant decreased reactivity despite the pronounced involvement of eos and M phi. This hyporeactive state persisted for greater than or equal to 4 weeks p.i..

Guinea pig airways isolated 4, 8 and 16 days (but not 2 days) after intra-tracheal inoculation with parainfluenza-3 virus In Vivo respond hyperreactive to contractile stimuli. In the present study it is shown that the virus-induced airway hyperresponsiveness is associated with a decreased Superoxide production by broncho-alveolar cells after additional stimulation with parainfluenza-3 virus.

Bronchial hyperreactivity to histamine 4 days following vaccination with the human respiratory pathogen Haemophilus influenzae was tested in two in vivo and one in vitro models. Conscious vaccinated guinea pigs exposed to aerosolized histamine became asphyxial significantly faster than saline-treated controls. Also the bronchoconstriction in anaesthetized guinea pigs as a result of i.v. histamine was significantly potentiated in the H. influenzae pretreated group. Isoprenaline (30 micrograms/kg) partially inhibited the bronchoconstriction. The difference in histamine sensitivity between the two groups however remained. Protection against bronchoconstriction by atropine on the other hand was significantly enhanced in the vaccinated animals. This suggests a hyperreactivity of the parasympathetic, cholinergic pathways as a result of H. influenzae vaccination.

Histamine produced a dose-dependent increase in heart rate, myocardial contractility and coronary flow in the isolated guinea-pig heart using a modified Langendorff procedure. Intraperitoneal treatment of the guinea pigs with E. coli endotoxin, 4 days prior to the experiment, enhanced the positive chronotropic and flow-increasing effect of histamine. The increased response to histamine appeared to be H1-receptor mediated, the positive chronotropic response is attributed to H2-receptors. These results indicate that bacterial endotoxin increases the reactivity of the coronary vascular system of the guinea-pig to histamine.

Respiratory histaminergic and cholinergic receptor function was investigated in isolated tracheal spirals of guinea pigs receiving different diets. Comparison was made between saline treated (controls) and Haemophilus influenzae treated animals in non sensitized conditions, the latter being a model for bronchial hyperreactivity, and in sensitized conditions, being a model for allergen induced bronchial hypersensitivity. The different semi-synthetic diets (35 energy% fat), varying in linoleic acid content (5.85, 11.25 and 22.05 en% fat) and one diet with low linoleic acid (3.55 en%) in which linolenic acid was added additionally (5.30 en%), exerted profound effects on tracheal reactivity to histamine. In sensitized animals the maximal induced histamine contraction was significantly diminished in the dietary group receiving 5.85 en% linoleic acid as compared with the other dietary groups (35% decrease in the H. influenzae-treated, 20-30% decrease in saline treated animals). Results in non-sensitized animals were similar, though less pronounced. No effect on food intake or growth of the animals could be demonstrated during the six week experimental periods. The carbachol induced contraction of the tracheal spirals of sensitized animals receiving low linoleic acid was also significantly decreased as compared to the other dietary groups (30% for saline treated and 20-30% for H. influenzae-treated animals). No difference in carbachol responsiveness could be detected between the different dietary groups under non-sensitized conditions. The results are discussed in view of the current concepts for bronchial hyperreactivity, especially in relation to eicosanoid involvement.

In rats, the vertebral artery make only a minor contribution to the blood perfusion of the ponto-medullary area. This was measured with radioactive microspheres and was confirmed by methylmetacrylate casts and local injection of a centrally acting hypotensive drug.