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M H Vargas

Publications and source records attributed to M H Vargas.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ozone-induced stimulation of pulmonary sympathetic fibers: a protective mechanism against edema.

Tropospheric ozone exerts well-described toxic effects on the respiratory tract. Less documented, by contrast, is the ability of ozone to induce protective mechanisms against agents that are toxic to the lungs. In particular, interactions between ozone and the sympathetic nervous system have never been considered. Using a model of permeability edema in isolated perfused rabbit lungs, we report here that, immediately after exposure of rabbits to 0.4 ppm ozone for 4 hr, the pulmonary microvascular responses to acetylcholine and substance P are completely blocked. Several lines of evidence, including partial inhibition of the ozone-induced protective effect by several drugs (alpha2- and beta-adrenergic antagonists, neuropeptide Y antagonist, guanethidine), measured levels of released catecholamines in blood and urine and the in vitro response of isolated lungs exposed to 0.4 ppm ozone all seem to suggest that ozone can stimulate pulmonary adrenergic fibers and induce the local release of catecholamines and neuropeptide Y, this resulting in transient protection against pulmonary edema. We also showed that, 48 hr after the exposure, ozone increased the baseline microvascular permeability and the response to low concentrations of acetylcholine.

Acetylcholine↗
PubMed1997

Effect of different ozone concentrations on the neurogenic contraction and relaxation of guinea pig airways.

Prejunctional and postjunctional effects of several ozone (O3) concentrations, including those found in highly polluted cities, were evaluated in guinea pig airways. Animals bred in O3-free conditions were exposed to air or O3 (0.3, 0.6 or 1.2 ppm) during 4 h, and studied 16-18 h later. Tracheal and bronchial rings were studied in organ baths. Electrical field stimulation (EFS) (100 V, 2 ms, 10 s) was given at increasing frequencies (0.25-16 Hz). Some tissues received atropine (2 microM) and/or propranolol (10 microM). Concentration-response curves to carbachol, isoproterenol, nitroprusside, and substance P were constructed. In tracheas, almost all O3 concentrations decreased the relaxation at low EFS frequencies, but had no effect on the propranolol-resistant (i-NANC) relaxation, suggesting that only adrenergic relaxation was affected. This was a prejunctional effect, since O3 did not modify the responses to isoproterenol. Relaxation induced by a nitric oxide (NO) donor, nitroprusside, was not affected by O3, which agrees with the lack of O3-effect on i-NANC system. O3 did not modify the EFS-induced e-NANC contraction in atropine-treated bronchi, nor the contraction caused by exogenous substance P. By contrast, in bronchi without atropine, 1.2 ppm O3 increased the e-NANC contraction induced by the highest EFS (16 Hz). O3 increased the maximum responses to carbachol in tracheas (1.2 ppm) and bronchi (0.6 and 1.2 ppm). In conclusion, we found that: a) O3 decreased adrenergic relaxation in guinea pig tracheas at low EFS frequencies through a prejunctional alteration; b) O3 did not modify the i-NANC relaxation in tracheas, at least the NO-mediated; c) O3 added a cholinergic component to the bronchial slow-phase (e-NANC) contraction evoked by EFS; and d) O3 enhanced the cholinergic responses in trachea and bronchi by a postjunctional mechanism.

Adrenergic Fibers↗
PubMed1995

Inhaled Bordetella pertussis vaccine decreases airway responsiveness in guinea pigs.

Bordetella pertussis (BP) has been used as adjuvant for experimental animal immunization, but its effects on airway responsiveness are uncertain. Three groups of guinea pigs were used: animals with a single exposure to inhaled BP vaccine (strain 134, total dose 1.24 x 10(12) germs), animals submitted to a sensitization procedure through inhalation of ovalbumin plus BP, and healthy control animals. Four weeks after inhalation of BP or after the beginning of sensitization, dose- or concentration-response curves to histamine were constructed in vivo and in vitro (tracheal and parenchymal preparations). We found that BP alone produced lower responses to histamine than control guinea pigs in vivo (insufflation pressure, p = 0.0003) and in tracheal tissues (p = 0.04), but not in parenchymal preparations. Sensitization did not modify the responsiveness compared with their respective controls. These results suggest that some BP component(s), probably pertussis toxin, causes a long lasting airway hyporesponsiveness in guinea pigs.

Adjuvants, Immunologic↗
PubMed1994

Effect of ozone exposure on antigen-induced airway hyperresponsiveness in guinea pigs.

Airway hyperresponsiveness can be induced by several stimuli including antigen and ozone, both of which may be present in the air of polluted cities. Though the effect of ozone on the bronchoconstrictor response to antigen has been well described, the combined effect of these stimuli on airway hyperresponsiveness has not yet been studied. Sensitized guinea pigs with or without ozone exposure for 1 h at 3 ppm, 18 h prior to study, were challenged with a dose-response curve to histamine (0.01-1.8 micrograms/kg, iv) followed by an antigen challenge (ovalbumin, 50 micrograms/kg, iv), and then by a second histamine dose-response curve 1 h later. Airway responses were measured as the increase in pulmonary insufflation pressure. In sensitized guinea pigs, the histamine ED50 significantly decreased after antigen challenge, demonstrating the development of airway hyperresponsiveness. Sensitized guinea pigs exposed to ozone showed airway hyperresponsiveness to histamine when compared with nonexposed animals, and such hyperresponsiveness was further enhanced after antigen challenge. We conclude that in this guinea pig model of acute allergic bronchoconstriction both antigen challenge and ozone induce airway hyperresponsiveness, while ozone exposure does not modify the development of antigen-induced hyperresponsiveness.

Acute Disease↗
PubMed1992

O3-induced airway hyperresponsiveness to noncholinergic system and other stimuli.

The effect of O3 exposure (3 ppm, 1 h) on the in vivo and in vitro airway responsiveness, as well as the changes in cell contents in bronchoalveolar lavage (BAL) fluid, were evaluated 16-18 h after O3 exposure in sensitized and nonsensitized male guinea pigs. The sensitization procedure was performed through repeated inhalation of ovalbumin for 3 wk. Increase in pulmonary insufflation pressure produced by the excitatory nonadrenergic noncholinergic (eNANC) system, histamine, and antigen were assessed in in vivo conditions, whereas airway responsiveness to histamine and substance P was evaluated in in vitro conditions by use of tracheal chains with or without epithelium and lung parenchymal strips. We found that O3 exposure 1) increased the neutrophil content in BAL fluids in both sensitized and nonsensitized guinea pigs, 2) caused hyperresponsiveness to eNANC stimulation in nonsensitized guinea pigs (although combination of sensitization and O3 exposure paradoxically abolished the hyperresponsiveness to eNANC stimulation), 3) increased the in vivo bronchoconstrictor responses to histamine and antigen, 4) caused hyperresponsiveness to substance P in nonsensitized tracheae with or without epithelium and in sensitized tracheae with epithelium, 5) did not modify the responsiveness to histamine in tracheae with or without epithelium (and in addition, epithelium removal caused hyperresponsiveness to histamine even in those tracheae exposed to O3), and 6) produced hyperresponsiveness to histamine in lung parenchymal strips either from sensitized or nonsensitized guinea pigs.

Animals↗
PubMed1990

Pharmacological characterization of mediators and vagal influence in the acute allergic bronchoconstriction in guinea pigs.

The allergic bronchoconstriction in guinea pigs has been attributed mainly to the release of mast cell mediators. Histamine has been involved in the first minutes of the anaphylactic reaction and new-formed compounds in the subsequent response. In this asthma model the vagal influence has been sparsely investigated. In the present work we evaluated the pharmacological modification of the acute allergic bronchoconstrictor response in guinea pigs sensitized to ovalbumin through aerosol exposure. Pyrilamine (20 micrograms/kg), diethylcarbamazine (a lipoxygenase inhibitor, 10 mg/kg) and dexamethasone (4 mg/kg) each reduced the antigen-induced bronchoconstriction throughout the 30 min studied. Indomethacin (3.1 mg/kg) did not modify the response to the antigen. Atropine (2 mg/kg) plus bilateral vagotomy also diminished this response from 5 min onward. On the other hand, from 5 min ahead pyrilamine-resistant bronchoconstriction was partially inhibited by dexamethasone, and it was almost completely blocked during all of the response when atropine plus bilateral vagotomy were added to dexamethasone. Dipyridamole (an inhibitor of the adenosine uptake, 0.4 mg/kg) enhanced the bronchoconstriction, though this was significant only in the 2-5 min time-interval of the response. These results suggest that histamine and vagal influence play an important role in the whole response to antigen, that other mediators, probably leukotrienes, participate in this response from 5 min onward, and that adenosine could exert a potentiation effect on this response.

Adenosine↗
PubMed1990

Lack of local neurogenic involvement in the hyperreactivity induced by epithelium removal in guinea pig trachea.

Airway epithelium removal produces tracheobronchial smooth muscle hyperreactivity to different constrictor agonists. Aside from the loss of an epithelium-derived relaxant factor, other mechanisms such as production of local axon reflex could hypothetically be involved. In the present work we investigated the effect of nerve activity inhibition or ganglionic transmission blockade in the epithelium removal-induced hyperreactivity in guinea pig trachea. Tetrodotoxin, tetracaine or hexamethonium did not modify the enhanced sensitivity of denuded tracheas to histamine, suggesting that, at least under these experimental conditions, local axon or ganglionic reflexes are not involved.

Animals↗
PubMed1988

Role of airway epithelium on the reactivity of smooth muscle from guinea pigs sensitized to ovalbumin by inhalatory method.

It has been demonstrated that the lack of epithelium in healthy airways from different species modifies the reactivity of tracheobronchial smooth muscle. In the present work we have investigated the effect of airway epithelium removal in tracheal chains from guinea pigs sensitized to ovalbumin by inhalatory route and unsensitized animals. We found that in both groups the mechanical removal of airway epithelium produced an increase in the tracheal sensitivity and maximum contractile response to histamine. The greatest responses were observed in epithelium-lacking sensitized tracheas. These findings, at least in vitro, support the idea that the damage of respiratory epithelium plays an important role in modulating the airway reactivity and this is more noteworthy in tracheal chains from previously sensitized guinea pigs.

Animals↗
PubMed1987

Possible role of leukotrienes in propranolol-induced airway hyperreactivity in sensitized guinea-pigs.

In anesthetized guinea-pigs previously sensitized to ovalbumin by intratracheal immunization, the intravenous administration of propranolol (3.1 mg/kg) produced an increase in the respiratory insufflation pressure induced by ovalbumin. Atropine (2 mg/kg), zolertine (1 mg/kg) and indomethacin (3.1 mg/kg) did not antagonize the propranolol-induced airway hyperreactivity. Indomethacin at higher dose (10 mg/kg) and BW755c (10 mg/kg) decreased the potentiation of the respiratory insufflation pressure to ovalbumin. Our results suggest that besides the beta-blockade, propranolol-induced bronchial hyperreactivity to ovalbumin in sensitized guinea-pigs could be mediated by leukotrienes.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMedDate not supplied

Ozone induces impairment of adrenergic relaxation in thoracic guinea pig tracheas.

The effect of ozone on airway relaxation mechanisms has been seldom studied. We exposed guinea pigs to ozone (0.3, 0.6 or 1.2 ppm for 4 h) and studied the in vitro tracheal responses to isoproterenol and nitroprusside, looking for differences between cervical and thoracic regions. We found that ozone did not alter responses to nitroprusside, whereas it produced a concentration-dependent decrease in the responses to isoproterenol in thoracic but not cervical tracheas. Thus, in isolated organ studies care should be taken to avoid mixing cervical and thoracic tracheal regions, at least when adrenergic responses are to be evaluated.

Animals↗
PubMedDate not supplied

Efficacy of human recombinant DNase in pediatric patients with cystic fibrosis.

BACKGROUND: Most respiratory complications in cystic fibrosis (CF) arise from abnormally viscid mucus, and rhDNase has shown to be effective in enhancing mucous clearance. We explored the responses to rhDNase in a Mexican population of CF patients. METHODS: Patients with CF received aerosolized rhDNase (2.5 mg daily) during 3 months, followed by daily aerosolized placebo during 3 months. RESULTS: A total of 21 CF patients entered the study (11.1 +/- 0.5 years of age, mean +/- SEM, 10 girls): 15 patients (71%) had basal forced vital capacity (FVC) higher than the 70% predicted value, and the remainder of the patients had an FVC of between 30 and 70%. As a group, rhDNase progressively increased the forced expiratory flow at 1 sec (FEV1) as well as the FVC, reaching statistical significance (p <0.005) at the end of the third month of treatment. Sputum production and difficulty to expectorate or to breathe also improved during the rhDNase treatment period (p <0.05 to p <0.001). All these changes progressively decreased to basal values after 3 months with aerosolized placebo. Adverse reactions were almost null, with a sole patient reporting dysphonia. CONCLUSIONS: Aerosolized rhDNase was effective in progressively improving respiratory function and symptoms in most CF patients.

Child↗
PubMedDate not supplied

Inflammatory cells and ferruginous bodies in bronchoalveolar lavage in urban dogs.

OBJECTIVE: To investigate whether high levels of atmospheric pollution modify the inflammatory cell count of the canine lung and to detect the presence of ferruginous bodies (FB) in the respiratory system. STUDY DESIGN: Bronchoalveolar lavage (BAL) was performed on dogs from four different areas of Mexico City and a rural area. With the BAL fluid recovered, total and differential cell counts were made, and ferruginous bodies were isolated by sodium hypochlorite digestion. They were counted by light microscopy and evaluated as a marker of exposure to particulate pollutants. RESULTS: There was no significant difference in the total cell count or in the macrophage number between the five groups. The neutrophil count was statistically higher in dogs from the southwest area as compared to the northeast and rural areas (P < .05). The lymphocyte count was significantly greater in the southwest, also. The northeast part of the city showed the highest number of FB in BAL fluids. CONCLUSION: The most polluted areas, in terms of particulate matter, were the northeast and the northwest; those are the locations of heavy industry. In contrast, in the southwest, where more inflammation was seen, the highest levels of ozone were registered during the year.

Animals↗
PubMedDate not supplied

[Prevalence of asthma in schoolchildren from the Mexican city Hermosillo].

Asthma is a very common disease, but its prevalence greatly varies from region to region, even in the same country. In the northwest of Mexico there is a lack of epidemiological studies on this disease. In this work a standardized questionnaire (ISAAC) was applied to parents of children attending 8 primary schools in the Mexican city of Hermosillo, Sonora. Of 3000 questionnaires sent, 1489 (49%) were acceptably answered. Children were of either sex and 9.1 +/- 1.8 years old (mean +/- SD). From this population, 74 (10.4%) out of 713 male and 67 (8.6%) out of 776 female children had an affirmative response to que question "Have you ever had asthma?", from which we conclude that global prevalence of asthma in the studied sample was 9.5%, an intermediate figure among those reported from other studies performed in Mexico.

Asthma↗
PubMedDate not supplied

Propranolol-induced hyperreactivity in guinea-pig lung parenchyma strips: possible role of histamine.

In vivo and in vitro studies have demonstrated that beta-adrenoceptor blockers enhance the airway smooth muscle contraction to antigen, but the mechanisms are not fully understood. In the present work, we corroborated that propranolol (3.9 x 10(-6) M, 30 min incubation) induces hyperreactivity to antigenic challenge (cumulative concentration-response curve to ovalbumin, 0.01 to 100 micrograms/ml) in lung parenchyma strips from sensitized guinea-pigs. This hyperreactivity was enhanced by indomethacin (3.2 x 10(-5) M) and was unaffected by the lipoxygenase/cyclooxygenase inhibitor phenidone (1 x 10(-4) M). However, the histamine H1 receptor antagonist pyrilamine (1 x 10(-6) M) reduced the potentiation effect of propranolol. These results suggest that bronchoconstrictor prostaglandins, thromboxane A2 and leukotrienes, are not involved in the propranolol-induced lung parenchyma strips hyperreactivity to antigen in vitro, and that histamine may account, at least in part, for such propranolol effect.

Animals↗
PubMedDate not supplied

Role of leukotriene C4 and edema in the acute allergic bronchoconstriction in the guinea pig.

In vitro studies have suggested that leukotrienes are involved in acute allergic bronchoconstriction, though this has not been definitively corroborated yet in in vivo studies. On the other hand, edema production during antigenic challenge could be an additional factor favouring such bronchoconstriction. In the present work we quantified immunoreactive leukotriene C4 (iLTC4) concentrations in bronchoalveolar lavages during allergic bronchoconstriction induced by 1 mg/kg i.v. ovalbumin (OA) in immunized guinea pigs, as well as water content in guinea pig lung fragments obtained before and during this bronchoconstriction. We found that basal concentrations of iLTC4 (median 1.06 ng/ml) were not significantly modified at 2, 5 and 10 min (median 1.10, 0.29 and 1.37 ng/ml, respectively) of the bronchoconstrictor response. Water content in lung fragments did not change among non-immunized guinea pigs, immunized ones and at 15 min of bronchoconstriction (mean +/- SEM 79.32% +/- 0.18, 79.10% +/- 0.31 and 79.13% +/- 0.40%, respectively). In addition, isoproterenol (20 micrograms/kg, i.v.) rapidly reverted about 70% of the bronchoconstriction induced by a higher antigenic dose (OA, 3.1 mg/kg i.v.); residual obstruction was not associated with increased water content in lung fragments (78.13% +/- 0.43). These results suggest that in this model, acute allergic bronchoconstriction is not due to an increased iLTC4 release or to edema production, and that airway smooth muscle contraction is the main component of this response.

Animals↗