Responses Of Tracheal Smooth Muscle Research Articles

Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats

Objective: To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats. Methods: Rats were randomly divided into six groups: the control group, the asthmatic group, and the asthmatic groups treated with dexamethasone (1 mg/kg; oral gavage) or three doses of rosmarinic acid (0.5, 1, and 2 mg/kg; oral gavage). For induction of asthma, rats received intraperitoneal injections and inhalation of ovalbumin. After 21 days, bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses. Moreover, total and differential white blood cell counts were determined. Results: The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group. In addition, rosmarinic acid reduced white blood cell count and the percentages of eosinophils, monocytes, and neutrophils while increasing the percentage of lymphocytes. Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid. Conclusions: Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

Quercetin supplementation attenuates airway hyperreactivity and restores airway relaxation in rat pups exposed to hyperoxia.

Hyperoxia exposure of immature lungs contributes to lung injury and airway hyperreactivity. Up to now, treatments of airway hyperreactivity induced by hyperoxia exposure have been ineffective. The aim of this study was to investigate the effects of quercetin on hyperoxia-induced airway hyperreactivity, impaired relaxation, and lung inflammation. Newborn rats were exposed to hyperoxia (FiO2 > 95%) or ambient air (AA) for seven days. Subgroups were injected with quercetin (10 mg·kg-1·day-1). After exposures, tracheal cylinders were prepared for in vitro wire myography. Contraction to methacholine was measured in the presence or absence of organ bath quercetin and/or Nω-nitro-L-arginine methyl ester (L-NAME). Relaxation responses were evoked in preconstricted tissues using electrical field stimulation (EFS). Lung tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels were measured by enzyme-linked immunosorbent assay (ELISA). A P < 0.05 was considered statistically significant. Contractile responses of tracheal smooth muscle (TSM) of hyperoxic animals were significantly increased compared with AA animals (P < 0.001). Treatment with quercetin significantly reduced contraction in hyperoxic groups compared with hyperoxic control (P < 0.01), but did not have any effect in AA groups. In hyperoxic animals, relaxation of TSM was significantly reduced compared with AA animals (P < 0.001), while supplementation of quercetin restored the lost relaxation in hyperoxic groups. Incubation of preparations in L-NAME significantly reduced the quercetin effects on both contraction and relaxation (P < 0.01). Treatment of hyperoxic animals with quercetin significantly decreased the expression of TNF-α and IL-1β compared with hyperoxic controls (P < 0.001 and P < 0.01, respectively).The findings of this study demonstrate the protective effect of quercetin on airway hyperreactivity and suggest that quercetin might serve as a novel therapy to prevent and treat neonatal hyperoxia-induced airway hyperreactivity and inflammation.

Preliminary Mechanistic Study on the Trachea Smooth Muscle Relaxant Activity of Aqueous Leaf Extract of Tridax Procumbens in Male Wistar Rats.

ObjectivesAqueous leaf extract of Tridax procumbens (ALETP) has potent relaxant activity. However, this relaxant activity in respiratory smooth muscle remains uninvestigated. This study investigates the effect of ALETP on the contractile activity of tracheal smooth muscle (TSM) in adult male Wistar rats.MethodsTwelve male Wistar rats divided into 2 groups and were treated with either 100 mg/kg of ALETP (ALETP treatment group) or vehicle (distilled water; control group) through oral gavage for 4 weeks. Dose responses of TSM from the 2 groups to acetylcholine (10–9 to 10–5 M), phenylephrine (10–9 to 10–5 M), and potassium chloride (KCl; 10–9 to 10–4 M) were determined cumulatively. Furthermore, cumulative dose responses to acetylcholine (10–9 to 10–5 M) after pre-incubation of TSM with atropine (10–5 M), L-NAME (10–4 M), indomethacin (10–4 M), and nifedipine (10–4 M), were determined.ResultsTreatment with ALETP substantially inhibited TSM contraction stimulated by cumulative doses of acetylcholine, phenylephrine, and KCl. Furthermore, preincubation of TSM from the 2 groups in atropine significantly inhibited contractility in TSM. Incubation in L-NAME and indomethacin also significantly inhibited contractility in TSM of ALETP-treated rats compared to that of controls. Contractile activity of the TSM was also inhibited significantly with incubation in nifedipine in ALETP-treated rats.ConclusionALETP enhanced relaxant activity in rat TSM primarily by blocking the L-type calcium channel and promoting endothelial nitric oxide release. ALETP contains agents that may be useful in disorders of the respiratory tract.

Quercetin Reverses the Enhanced Contractile Responses of Tracheal Smooth Muscle of Neonatal Rats Exposed to Hyperoxia

Neonatal hyperoxia increases contraction and decreases the relaxation of airway smooth muscle (ASM), and the balance between these processes in airways is critical for normal flow of air. Thus, it is important to search for an effective treatment to prevent the airway hyperreactivity. Therefore, we tested the hypothesis that supplementation of quercetin will overcome the enchanced contractile responses of tracheal smooth muscle exposed to hyperoxia. Tracheal cylinders were obtained from Wistar rat pups (P12) exposed to hyperoxia (≥ 95% O2) or room air for seven days. These cylinders were used to study contractile responses of ASM evoked by methacholine (MCh, 10‐8 – 10‐4 M) in absence or presence of quercetin (100 μM). MCh induced dose‐dependent contractile responses of ASM. Hyperoxic exposure significantly increased the contractile responses of ASM towards MCh, as compared to those obtained from control animals exposed to room air, and these enhanced contractile responses in hyperoxic tissues were significantly attenuated in presence of quercetin. The results of this study revealed that quercetin reverses the enhanced contractile responses of airway smooth muscle induced by hyperoxic exposure and we speculate that the use of quercetin might be an effective therapeutic approach to prevent the airway hyperreactivity induced by hyperoxia.Support or Funding InformationSupported by MEST

Resveratrol Protects Against Hyperoxia‐Induced Airway Hyperreactivity in Neonatal Rats

Neonatal hyperoxia is associated with airway hyperreactivity and lung injury. We tested the hypothesis that supplementation of resveratrol will overcome the increased contractile responses of tracheal smooth muscle exposed to hyperoxia. Tracheal cylinders were obtained from Wistar rat pups (P12) exposed to hyperoxia (≥ 95% O2) or room air for seven days. These cylinders were used to study contractile responses of airway smooth muscle (ASM) evoked by methacholine (MCh, 10‐8 – 10‐4 M) in absence or presence of resveratrol (100 μM). MCh induced dose‐dependent contractile responses of ASM. The contractile responses towards MCh were significantly higher in preparations obtained from animals exposed to hyperoxia as compared to those obtained from control animals exposed to room air. The enhanced contractile responses in hyperoxic tissues were significantly attenuated in presence of resveratrol. The results of this study revealed that resveratrol diminishes the airway hyperreactivity induced by hyperoxia and we speculate that the use of resveratrol might be an effective therapeutic approach to prevent the adverse effects of hyperoxia.Support or Funding InformationSupported by MEST

The protective effect of α-hederin, the active constituent of Nigella sativa, on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

Many investigations have demonstrated the prophylactic effect of Nigella sativa on asthma disease. One of its active constituents is α-hederin. In the present study, the preventive effect of two different concentrations of α-hederin on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs was examined. Forty male adult Dunkin-Hartley guinea pigs were randomly divided into the control (C), sensitized (S) and sensitized pretreated groups with thymoquinone (3 mg/kg i.p., S + TQ), low-dose α-hederin (0.3 mg/kg i.p., S + LAH) and high-dose α-hederin (3 mg/kg i.p., S + HAH). The responsiveness of tracheal smooth muscle (TR) to methacholine, histamine and ovalbumin was assessed. Moreover, total and differential white blood cell counts in lung lavage fluid were examined. Compared with the S group, the mean EC50 value in the S + LAH group increased significantly (p < 0.05). The mean EC50 value of histamine contraction in the S + LAH and S + HAH groups was significantly higher than in the S group (p < 0.05). In all pretreated groups, the TR to ovalbumin decreased in comparison to the S group (p < 0.001). Both the S + HAH and S + LAH groups showed significantly decreased TR compared to the S + TQ group (p < 0.01-p < 0.01). Total WBC and eosinophil counts in all pretreated groups decreased significantly in comparison with the S group (0.001-0.01). There was a significant increase in neutrophil, lymphocyte and monocyte counts in the pretreated groups compared to the S group (p < 0.001-p < 0.05). The basophil count in the S + TQ and S + HAH groups was significantly lower than in the S group (p < 0.01-p < 0.05). This study suggested that α-hederin has anti-inflammatory and bronchodilatory effects like thymoquinone.

Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein

The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30μM) were markedly smaller in VIRUS segments compared to SHAM segments (2±1% relaxation vs. 28±5%, n=14, p<0.01). Similarly, relaxation responses of VIRUS segments to the neuropeptide substance P (SP) were greatly attenuated (1±1% vs. 47±6% evoked by 1nM SP, n=14, p<0.001). Consistent with epithelial damage, PGE2 release in response to both acrolein and SP were reduced in VIRUS segments (>35% reduction, n=6, p<0.01), as determined using ELISA. In contrast, exogenous PGE2 was 2.8-fold more potent in VIRUS relative to SHAM segments (−logEC50 7.82±0.14 vs. 7.38±0.05, n=7, p<0.01) whilst responses of VIRUS segments to the β-adrenoceptor agonist isoprenaline were similar to SHAM segments. In conclusion, relaxation responses evoked by acrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection.

Study of the interaction of glutamatergic and nitrergic signalling in conditions of the experimental airways hyperreactivity

BackgroundGlutamatergic and nitrergic system participate in the control of respiratory system functions. It is only little information regarding a possible interaction of both systems in the airways hyperractivity. We investigated the effect of agents modulating the activity of these systems on the experimental ovalbumin-induced airways hyperreactivity as well as on the changes of exhaled nitric oxide (eNO) levels. MethodsWe used the agonists of NMDA receptors – N-methyl-D-aspartic acid (NMDA) and monosodium glutamate (MSG), selective competitive antagonist (DL-2-amino-5-phosphonovaleric acid – AP-5) and selective non-competitive antagonist (dizocilpine – MK-801) of these receptors. We used also non-specific inhibitor of NO synthases Nω-nitro-L-arginine methyl ester (L-NAME). The airways responsiveness to histamine or acetylcholine was evaluated under in vitro conditions. ResultsNMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. The effect of MSG was less pronounced. MK-801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle. We recorded the changes in eNO levels. The activation of NMDA receptor with NMDA or MSG increased eNO levels. The inhibition of NO synthase with L-NAME caused the fall of eNO levels. MK-801 shows (within the group) the more expressive effect in the eNO levels during sensitization than AP-5 group. ConclusionThe results confirm the possibility of NMDA receptors participation in the experimental airways hyperreactivity.

Bronchodilatory effect of ethanolic extract of the leaves of Nyctanthes arbortristis

Background:Nyctanthes arbortristis has been used in traditional medicine for the treatment of asthma and cough.Aim:In this study, bronchodilatory effect of ethanolic extract of the N. arbortristis was investigated under in vitro conditions. The concentration–response curve of the tracheal smooth muscle (TSM) to histamine was recorded in presence or absence of ethanolic extract and Nω-nitro-l-arginine methyl ester (L-NAME). Dose–response effect of ethanolic extract on pre-constricted tissues was investigated. The ethanolic extract inhibited the histamine-induced maximum contractile responses of TSM (P < 0.001). Ethanolic extract also cause dose-dependent relaxation of TSM. These effects were reversed by L-NAME. Phytochemical analysis showed the presence of typical plant constituents. These results suggest the possible use of extract of the leaves of N. arbortristis as a bronchodilator in therapeutic treatment of asthma.

Trans-Caryophyllene, a Natural Sesquiterpene, Causes Tracheal Smooth Muscle Relaxation through Blockade of Voltage-Dependent Ca2+ Channels

trans-Caryophyllene is a major component in the essential oils of various species of medicinal plants used in popular medicine in Brazil. It belongs to the chemical class of the sesquiterpenes and has been the subject of a number of studies. Here, we evaluated the effects of this compound in airway smooth muscle. The biological activities of trans-caryophyllene were examined in isolated bath organs to investigate the effect in basal tonus. Electromechanical and pharmacomechanical couplings were evaluated through the responses to K+ depolarization and exposure to acetylcholine (ACh), respectively. Isolated cells of rat tracheal smooth muscle were used to investigate trans-caryophyllene effects on voltage-dependent Ca2+ channels by using the whole-cell voltage-clamp configuration of the patch-clamp technique. trans-Caryophyllene showed more efficiency in the blockade of electromechanical excitation-contraction coupling while it has only minor inhibitory effect on pharmacomechanical coupling. Epithelium removal does not modify tracheal smooth muscle response elicited by trans-caryophyllene in the pharmacomechanical coupling. Under Ca2+-free conditions, pre-exposure to trans-caryophyllene did not reduce the contraction induced by ACh in isolated rat tracheal smooth muscle, regardless of the presence of intact epithelium. In the whole-cell configuration, trans-caryophyllene (3 mM), inhibited the inward Ba2+ current (IBa) to approximately 50% of control levels. Altogether, our results demonstrate that trans-caryophyllene has anti-spasmodic activity on rat tracheal smooth muscle which could be explained, at least in part, by the voltage-dependent Ca2+ channels blockade.

Substance P Regulates Environmental Tobacco Smoke-Enhanced Tracheal Smooth Muscle Responsiveness in Mice

Environmental tobacco smoke (ETS) is an environmental trigger that leads to airway inflammation and airway hyperresponsiveness (AHR) in susceptible individuals and animals, but the underlying mechanism is not fully understood. Substance P (SP) release from sensory nerve fibers has been linked to AHR. The present experiments characterize the role of SP in tracheal smooth muscle on ETS-increased airway responses. The mice were exposed to either sidestream tobacco smoke (SS), a surrogate to ETS, or filtered air (FA) for 1 day or 5 consecutive days. Contractions of tracheal smooth muscle to SP and electrical field stimulation (EFS) were not significantly altered in 1 of day SS-exposed mice. However, 5 of days SS exposure significantly increased airway smooth muscle contractions to SP and EFS. Administration of CP-99994, an antagonist of the neurokinin (NK)1 receptor, attenuates the SS exposure-enhanced tracheal smooth muscle responses to EFS. Furthermore, the immunohistochemistry showed that SP nerve fibers were increased in tracheal smooth muscle after 5 of days SS exposure. These results suggest that the increased SP production may contribute to SS-enhanced smooth muscle responsiveness in mice trachea.

Glutamate receptors and the airways hyperreactivity

It is proposed the link between the hyperactivity of NMDA receptors and airway hyperresponsiveness. We investigated the effect of agents modulating the activity of NMDA receptors in the ovalbumin-induced airway hyperreactivity in guinea pigs. The airways hyperreactivity was influenced by the agonist (NMDA) and selective antagonist - competitive (AP-5) and non-competitive (MK-801) of NMDA receptors. Airway responsiveness to histamine or acetylcholine was evaluated in in vitro conditions. NMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. MK 801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle, while the former, non-competitive antagonist was more effective. We recorded more pronounced response in tracheal than in lung tissue smooth muscle with more considerable response to acetylcholine than to histamine. The results of experiments show the modification of airway smooth muscles responses by agents modulating the activity of NMDA receptors. They confirm the possibility of NMDA receptors participation in experimental airway hyperreactivity. The results enlarge information regarding the link of the inflammatory diseases and glutamatergic system.

The efficiency of polyphenolic compounds on allergen induced hyperreactivity of the airways

The results of some epidemiologic studies have suggested that the consumption of the food containing polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effect of the 21-day red-wine polyphenolic compounds (Provinol) administration on allergen (OVA) induced inflammation of the airways in experimental conditions. The allergic inflammation of the airways was induced in guinea pigs by 21-day ovalbumin sensitization. The tracheal smooth muscle reactivity was examined by in vitro method to bronchoconstricting mediator histamine (10 −8–10 −3 mol/L); the changes in airways resistance were examined by in vivo method by exposure to nebulized histamine (10 −6 mol/L). The histological investigation of the tracheal tissue and BALF levels of IL-4, IL-5 were used as parameters of the airway inflammation. A 21-day administration of Provinol caused a significant decrease of the specific airway resistance after the histamine nebulization and the decline in tracheal smooth muscle contraction amplitude to this bronchoconstrictor. Provinol minimized the degree of inflammation estimated on the basis of eosinophil calculation and levels of inflammatory cytokines IL-4 and IL5. In conclusion, the administration of Provinol leads to bronchodilating and anti-inflammatory effects in ovalbumin-sensitized guinea pigs, suggesting their possible use in the therapy of allergic inflammatory conditions of the airways.

L‐Citrulline Protects Against Hyperoxia‐Induced Increase in Airway Contractile Responses

Neonatal hyperoxia increases contraction and decreases relaxation of airways in rat pups due to upregulation of arginase activity and decrease of L‐arginine bioavailability to nitric oxide synthase (NOS). Therefore, we tested the hypothesis that supplementation of L‐citrulline will overcome the increased contractile responses of tracheal smooth muscle (TSM) induced by hyperoxia. Tracheal cylinders were excised from rat pups 12 days old, exposed to hyperoxia or room air for seven days. To induce contraction of TSM, electrical field stimulation (EFS) was applied. Hyperoxia increased EFS‐induced contractile responses as compared to room air animals (1.29 ± 0.1 g vs. 0.83 ± 0.2 g). In vitro supplementation of L‐citrulline decreased the contractile responses in hyperoxic group, but did not show any effect in control group under basal conditions. Inhibition of enzymes involved in L‐citrulline recycling prevented this effect of L‐citrulline. Inhibition of NOS, increased airway contraction in control group but did not affect the responses in hyperoxic group. Incubation with exogenous L‐citrulline reversed the increased contractility.These data demonstrate that L‐citrulline/L‐arginine cycle is effective in TSM under conditions of reduced L‐arginine bioavailability to NOS. In vitro supplementation of L‐citrulline reverses the increased contractile responses in hyperoxic animals to control levels.

The Effect of Ethanol on Tracheal Smooth Muscle During Maturation

In previous studies we have shown that ethanol induces contraction of pulmonary artery smooth muscle in dog. Ethanol induced also contraction of tracheal smooth muscle (TSM) in adult animals. However, the effect of ethanol during development is not well understood. Therefore, we hypothesize that ethanol induces contraction during whole postnatal life. The experiments were performed on TSM strips obtained form piglets and young pigs at three ages (3–7 days, 2–3 wk and 3 mo.). After anesthesia, the trachea was removed and tracheal strips were prepared, and placed in organ baths, filled with Krebs-Henseleit solution to equilibrate. Tissues were challenged with different concentration of ethanol (46–276 mM). The role of extra-cellular Ca2+ was studied by incubation of tissues in KH solution with presence or absence of Ca2+or using a Ca2+ channel blocker, nifedipine (10, 50, 100 μM). Ethanol induced concentration-dependent contraction of TSM at three ages. The absence of Ca2+ in extra-cellular environment reduced TSM tone in response to ethanol. Also, blockade of Ca2+ channels reduced contractile responses of TSM and the extent of this reduce depended from the concentration of nifedipine. Based on the results of this study we conclude that ethanol induces TSM contraction in piglets and this effect disclose since the birth. extra-cellular Ca2+ plays an important role on TSM tone in response to ethanol.

Competition of NO synthases and arginase in the airways hyperreactivity

The competition between arginases and NO synthases (NOS) for their common substrate L-arginine can be important in the airways hyperreactivity. We investigated the effect of the simultaneous modulation of arginase and NOS activities in allergen-induced airways hyperreactivity. We analysed the response of tracheal and lung tissue smooth muscle to histamine or acetylcholine after administration N(ω)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and N(ω)-hydroxy-L-arginine (NOHA) in the combinations in in vitro conditions. The results show the decrease of ovalbumin-induced hyperreactivity after inhibition of arginase activity with NOHA. A supplementation of L-arginine caused favourable effect on the airway smooth muscle response. We found the airway reactivity decrease on the whole if we used the combination of NOS and arginase inhibitors. The inhibition of both types of enzymes caused more expressive effect in tracheal smooth muscles. We recorded the difference in the response to histamine or acetylcholine. The simultaneous inhibition of iNOS (with AG) and arginase (with NOHA) evoked the most expressive effect. Results show the importance of competition of both types enzymes - NOS and arginase for the balance of theirs activities in the control of airways bronchomotoric tone in the conditions of the airways hyperreactivity.

Effects of 3-methylhistamine and phenylethylamine on histamine action on isolated guinea-pig trachea rings

It is well known that histamine produces constriction via H1 receptors and decreases tracheal smooth muscle tone via H2 and H3 receptors. In addition, it has already been reported that 3-methylhistamine and phenylethylamine are competitive antagonists of histamine N-methyl-transferase (HMT), the enzyme responsible for rapid inactivation of histamine. Our results suggest the possibility that 3- methyl-histamine and phenylethylamine as competitive antagonists of histamine N-methyl-transferase lead to potentiation of histamine induced constriction of isiolated guinea-pig trachea, probably due to the decrease of histamine methylation and consequent inactivation. In as much, 3-methyl-histamine and phenylethylamine had no effect on the basal tone of isolated trachea smooth muscle, as well as on other mechanisms leading to increased responsiveness of guinea-pig tracheal smooth muscle (acetylcholine, KCl, electro stimulation).

Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig.

Aim:To explore the effect of montelukast on bradykinin-induced tracheal smooth muscle contraction of isolated guinea pig trachea.Study Design:To study the effect of bradykinin in the absence and in the presence of montelukast on the isolated tracheal smooth muscle of a guinea pig pretreated with indomethacin (10-6M), phentolamine (10-5M), and propranalol (10-6M), to eliminate the effect of endogenous prostaglandins and catecholamines. The trachealis smooth muscle activity was recorded through the Isometric Force Displacement Transducer on a Four Channel Oscillograph. A cumulative dose-response relationship was demonstrated by adding successive doses of bradykinin on the tracheal strips, starting with 11 μg to 77 μg of 10-4 concentration. A similar procedure was repeated in the presence of montelukast 0.5 μg/ml, which, was equal to approximate Cmax achieved in vivo with a 10 mg oral dose of montelukast, and in the presence of 1 μg/ml of montelukast.Statistical Analysis:Data was expressed as mean ± standard error (SEM), and was analyzed using the SPSS version 15. A P value of less than 0.05 was considered significant.Results:Bradykinin produced a dose-dependent, reversible contraction of isolated tracheal smooth muscle. Montelukast significantly reduced the bradykinin-induced tracheal smooth muscle reactivity and shifted the bradykinin curve to the right and downwards, in the presence of both concentrations of montelukast. The mean magnitude of response achieved with 77 μg of bradykinin in the absence of montelukast was 39 mm ± 6.26, in the presence of 0.5 μg/ml of montelukast it was 24.17 mm ± 4.11, and in the presence of 1 μg/ml of montelukast it was 13 mm ± 2.6.Conclusion:It is concluded that montelukast significantly inhibits, in a dose-dependent manner, the bradykinin-induced contraction of the guinea pig tracheal smooth muscle, and alludes to an interaction between the bradykinin and leukotriene mediators.

The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

OBJECTIVE:To examine the preventive effect of a hydro-ethanolic extract of Nigella sativa on the tracheal responsiveness and white blood cell count in the lung lavage fluid of sensitized guinea pigs.METHODS:Three groups of guinea pigs sensitized to intraperitoneally injected and inhaled ovalbumin were given drinking water alone (group S), drinking water containing a low concentration of N. sativa extract (group S+LNS) or drinking water containing a high concentration of N. sativa extract (group S+HNS). The tracheal responses of control animals (group C) and the three groups of sensitized guinea pigs (n = 7 for all groups) to methacholine were measured by the assessment of the tracheal smooth muscle response to increasing concentrations of methacholine, and the effective concentration causing 50% of the maximum response (EC50) was determined. Tracheal responses to 0.1% ovalbumin and white blood cell counts in the lung lavage fluid were also examined.RESULTS:The tracheal response of the group S guinea pigs to both methacholine and ovalbumin was significantly higher than the response of the controls (p<0.01 for both cases). The tracheal responses of the S+LNS and S+HNS groups to both methacholine and ovalbumin were significantly decreased compared to those of the S group (p<0.05 to p<0.01). The total white blood cell and eosinophil counts in the lung lavage fluid of group S were significantly higher than those of group C (p<0.01). The white blood cell counts in both treated groups showed significant improvements (p<0.01 for both cases).CONCLUSIONS:These results demonstrate the preventive effect of the N. sativa extract on the tracheal response and lung inflammation in sensitized guinea pigs.

The efficiency of polyphenolic compounds on allergen induced hyperreactivity of the airways

The results of some epidemiologic studies have suggested that the consumption of the food containing polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effect of the 21-day red-wine polyphenolic compounds (Provinol) administration on allergen (OVA) induced inflammation of the airways in experimental conditions. The allergic inflammation of the airways was induced in guinea pigs by 21-day ovalbumin sensitization. The tracheal smooth muscle reactivity was examined by in vitro method to bronchoconstricting mediator histamine (10 −8–10 −3 mol/L); the changes in airways resistance were examined by in vivo method by exposure to nebulized histamine (10 −6 mol/L). The histological investigation of the tracheal tissue and BALF levels of IL-4, IL-5 were used as parameters of the airway inflammation. A 21-day administration of Provinol caused a significant decrease of the specific airway resistance after the histamine nebulization and the decline in tracheal smooth muscle contraction amplitude to this bronchoconstrictor. Provinol minimized the degree of inflammation estimated on the basis of eosinophil calculation and levels of inflammatory cytokines IL-4 and IL5. In conclusion, the administration of Provinol leads to bronchodilating and anti-inflammatory effects in ovalbumin-sensitized guinea pigs, suggesting their possible use in the therapy of allergic inflammatory conditions of the airways.