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H Koto

Publications and source records attributed to H Koto.

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

Inducible nitric oxide synthase after sensitization and allergen challenge of Brown Norway rat lung.

1. We studied the effects of ovalbumin (OA) sensitization and challenge on inducible nitric oxide synthase (iNOS) gene and protein expression in Brown-Norway rats in vivo. 2. By use of Northern analysis, a 4.4-kb iNOS mRNA transcript was weakly observed in control rat lung but there was a 3 fold increase in lungs sensitized to OA alone (P<0.05). In sensitized rats, four hours after exposure to OA aerosol, there was a 6 fold increase in iNOS mRNA transcript (P<0.05), which returned to baseline at 24 h. 3. Immunostaining with an anti-mouse iNOS antibody revealed some patchy staining of airway epithelium in naive rats. There were no changes in sensitized rats exposed to saline, but sensitized and OA-exposed rats showed increased expression in iNOS staining in macrophages. 4. Electrophoretic mobility shift assays of lung nuclear extracts showed a marked increase in nuclear factor-kappaB (NF-kappaB)-binding activity at 2 h after allergen exposure with return to baseline at 6, 12 and 24 h. 5. We concluded that there is increased iNOS gene and protein expression associated with increased NF-kappaB DNA-binding in lungs of sensitized and challenged rats. The increase in iNOS expression may underlie the increase in exhaled NO found after allergen challenge and may contribute to the development of allergen-induced airway hyperresponsiveness.

Allergens↗
PubMed1997

The effects of a specific tachykinin receptor antagonist FK-224 on ozone-induced airway hyperresponsiveness and inflammation.

We have demonstrated previously that tachykinin depletion by capsaicin prevented the ozone-induced airway hyperresponsiveness and the bronchial wall oedema in guinea pigs. To further clarify the role of neurogenic inflammation in ozone-induced airway hyperresponsiveness, we investigated the effects of a specific tachykinin receptor antagonist (FK-224) in guinea pigs. Animals were anaesthetized, tracheostomized and mechanically ventilated. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and box flow in a plethysmograph. Airway responsiveness was assessed by determining the provocative concentration of histamine aerosol that increased RL to twice the baseline value (PC200). Animals were injected with either FK-224 (10 mg/kg, dissolved in 0.2 mL/kg DMSO) or vehicle (0.2 mL/kg DMSO) intravenously, then pre-ozone PC200 was determined. Following this measurement, animals were exposed to 3 ppm ozone for 60 min. Immediately after exposure, the histamine dose response curve was evaluated again. Bronchoalveolar lavage (BAL) was performed in animals treated with FK-224 or vehicle. In animals treated with vehicle, ozone exposure caused significant decrease in PC200 and moderate increase in neutrophils in BAL fluid. FK-224 pre-treatment significantly inhibited ozone-induced hyperresponsiveness. Neutrophils in BAL fluid did not significantly increase after ozone exposure in animals treated with FK-224. By contrast, the degree of epithelial desquamation did not differ significantly between the two groups. We conclude that neurogenic inflammation caused by tachykinin release may be responsible for ozone-induced bronchial hyperresponsiveness, and that tachykinins may play a role in the initiation of airway inflammation.

Airway Resistance↗
PubMed1997

Pre- and post-junctional effects of VIP-like peptides in guinea pig tracheal smooth muscle.

To determine the role of VIP-like peptides on neurotransmission of vagus nerve, we evaluated the effects of helodermin, helospectin, and vasoactive intestinal peptide (VIP) on the contraction of guinea pig tracheal smooth muscle evoked by electrical field stimulation (EFS) or the exogenous application of actylcholine (ACh). Isometric tension of tracheal strips was measured in the presence of indomethacin (10(-6) M) and of guanethidine (10(-6) M). VIP (10(-9) M to 10(-7) M) significantly suppressed the contraction evoked by EFS. VIP, at concentrations of 10(-9) M and 10(-8) M, did not affect the ACh-evoked contraction, but a concentration of 10(-7) M suppressed ACh-evoked contraction. Helospectin and helodermin (10(-8) M and 10(-7) M) significantly suppressed the EFS-evoked contraction, but 10(-9) M showed no effect. Helospectin and helodermin had no effect on the ACh sensitivity of smooth muscle up to 10(-8) M, but a concentration of 10(-7) M suppressed the ACh-evoked contraction. These results indicate that helodermin, helospectin, and VIP exert both pre- and post-junctional inhibitory effects on the airway smooth muscle of guinea pigs. These peptides, thus, inhibited tracheal smooth muscle contraction prejunctionally at low concentrations, and acted postjunctionally at higher concentrations.

Acetylcholine↗
PubMed1997

Interaction of ozone and allergen challenges on bronchial responsiveness and inflammation in sensitised guinea pigs.

BACKGROUND: Environmental pollutants such as ozone may interact with airway responses to allergen in sensitised individuals. METHODS: We examined the effects of a single exposure to ozone (1 ppm for 1 h) on bronchial responsiveness to acetylcholine (ACh) aerosol 3 and 24 h after single ovalbumin (OA) challenge in OA-sensitised anaesthetised guinea pigs. Broncho-alveolar lavage (BAL) was performed and protein content and differential cell counts were determined. RESULTS: Ozone increased bronchial responsiveness at 3 h but not at 24 h, while OA alone had no effect. At 3 h after ozone, OA induced further, but non-significant increases in bronchial responsiveness to ACh, but at 24 h after ozone, there was enhanced responsiveness. Neutrophil counts in BAL fluid increased at 3 and 24 h after exposure to ozone alone, but there were no further increases with ozone followed by OA exposure. Protein concentration was significantly increased in the ozone and OA groups at 3 and 24 h (163.4 +/- 25.6 and 128.7 +/- 7.4 mg/ml, respectively) compared to 54.0 +/- 18.1 mg/ml in the control group (p < 0.02 and p < 0.01, respectively). CONCLUSION: Our data demonstrate an interaction of OA with ozone exposure on bronchial responsiveness; one underlying mechanism could be through damage at the endothelial-epithelial barrier.

Acetylcholine↗
PubMed1997

Role of cytokine-induced neutrophil chemoattractant (CINC) in ozone-induced airway inflammation and hyperresponsiveness.

Cytokine-induced neutrophil chemoattractant (CINC) is a rat chemokine with potent chemoattractant effects on neutrophils. We determined the involvement of CINC in ozone-induced airway neutrophilia and bronchial hyperresponsiveness (BHR) in the rat. We found a marked increase in lung CINC messenger RNA (mRNA) within 2 h after cessation of ozone exposure (1 ppm for 3 h), as measured by Northern blot analysis, whereas rats exposed to room air had no detectable CINC mRNA. Ozone exposure induced a significant neutrophilia in bronchoalveolar lavage fluid (BALF) at 24 h after exposure (air-exposed rats: 4.2 +/- 2.0 x 10(4), versus ozone-exposed rats: 16.1 +/- 3.7 x 10(4)); prior treatment with a goat anti-CINC antibody (1 mg, intravenously) suppressed the neutrophilia (3.1 +/- 0.9 x 10(4)). When administered intratracheally, the antibody (230 micrograms) partially inhibited the influx of neutrophils. The increase in bronchial responsiveness to acetylcholine observed after ozone exposure was not inhibited by the anti-CINC antibody. The anti-CINC antibody (1 mg, intravenously) also inhibited BALF neutrophilia induced by exposure to a higher concentration of ozone (3 ppm, 3 h), without an effect on BHR. CINC is an important chemokine causing ozone-induced neutrophil chemoattraction, but is not involved in the induction of ozone-induced BHR. The neutrophil is unlikely to contribute to BHR in this model.

Acetylcholine↗
PubMed1996

Mechanisms of impaired beta-adrenoceptor-induced airway relaxation by interleukin-1beta in vivo in the rat.

We studied the in vivo mechanism of beta-adrenergic receptor (beta-AR) hyporesponsiveness induced by intratracheal instillation of interleukin-1beta (IL-1beta, 500 U) in Brown-Norway rats. Tracheal and bronchial smooth muscle responses were measured under isometric conditions ex vivo. Contractile responses to electrical field stimulation and to carbachol were not altered, but maximal relaxation induced by isoproterenol (10(-6)-10(-5) M) was significantly reduced 24 h after IL-1beta treatment in tracheal tissues and to a lesser extent, in the main bronchi. Radioligand binding using [125I]iodocyanopindolol revealed a 32+/-7% reduction in beta-ARs in lung tissues from IL-1beta-treated rats, without any significant changes in beta2-AR mRNA level measured by Northern blot analysis. Autoradiographic studies also showed significant reduction in beta2-AR in the airways. Isoproterenol-stimulated cyclic AMP accumulation was reduced by IL-1beta at 24 h in trachea and lung tissues. Pertussis toxin reversed this hyporesponsiveness to isoproterenol but not to forskolin in lung tissues. Western blot analysis revealed an IL-1beta-induced increase in Gi(alpha) protein expression. Thus, IL-1beta induces an attenuation of beta-AR-induced airway relaxation through mechanisms involving a reduction in beta-ARs, an increase in Gi(alpha) subunit, and a defect in adenylyl cyclase activity.

Animals↗
PubMed1996

Ozone induction of cytokine-induced neutrophil chemoattractant (CINC) and nuclear factor-kappa b in rat lung: inhibition by corticosteroids.

We determined in rat lung whether ozone exposure was associated with the expression of the chemokine, cytokine-induced neutrophil chemoattractant (CINC), and of the transcription factor, NF-kappa B. CINC mRNA expression peaked at 2 h after cessation of ozone exposure, and returned to basal levels by 24 h. DNA-binding activity of NF-kappa B showed a marked increase after ozone, maximal at 2 h. Dexamethasone inhibited CINC mRNA and NF-kappa B expression, together with neutrophilic inflammation. Our data supports the concept that ozone leads to NF-kappa B activation which increases CINC mRNA expression. These series of events could lead to neutrophilic inflammation.

Animals↗
PubMed1996

Thromboxane A2 mimetic (U-46619) induces hyperresponsiveness of smooth muscle in the canine bronchiole, but not in the trachea.

It has been reported that cholinergic agonists induce bronchoconstriction by directly stimulating M3 muscarinic receptors on the surfaces of smooth muscle cells. Although thromboxane A2 (TXA2) has been demonstrated to induce airway hyperresponsiveness to cholinergic agonists in vivo, it does not affect the contractile response of smooth muscle to cholinergic agonists in vitro. To investigate the causes for the discrepancy between the in vivo and in vitro data, we compared the effects exerted by a TXA2 mimetic, U-46619, on the smooth muscle of canine trachea and bronchiole. We measured the contractile response to exogenously applied acetylcholine (ACh) before and after the application of a subthreshold dose of U-46619. The subthreshold dose was determined as that dose which did not induce smooth muscle contraction, this being 10(-9) M in the present study. The contractile responses of tracheal strips to ACh were not affected by the subthreshold dose of U-46619. By contrast, the responses of bronchiolar rings were significantly enhanced by this subthreshold dose. The excitatory effect of U-46619 on the ACh-induced contraction was completely prevented by treatment with a TXA2 antagonist, BAY u3405. These results indicate that TXA2 directly increases the responsiveness of smooth muscle in the bronchiole, and suggest that increases in the responsiveness of small airways may play an important role in the development of the airway hyperresponsiveness induced by TXA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Thromboxane A2 antagonist inhibits leukotriene D4-induced smooth muscle contraction in guinea-pig lung parenchyma, but not in trachea.

Although the bronchoconstriction induced by leukotriene D4 (LTD4) has been reported to be partly mediated by thromboxane A2 (TXA2) in the guinea-pig airway, it is not known which part of the airway is susceptible to TXA2. In order to determine the role of TXA2 in the central and peripheral airways, we compared the effect of a TXA2 antagonist on tracheal strips to its effect on parenchymal strips of guinea-pigs. Tracheal and parenchymal strips were mounted in a 3.5 ml organ bath filled with Krebs-Henseleit solution aerated with 95% O2, 5% CO2 and kept at 37 degrees C. After equilibration for 60 min in Krebs solution, the strip was contracted by exposure to 10(-5) M of acetylcholine (ACh). Sixty minutes after ACh was eliminated, the concentration-response curve to LTD4 (10(-9) M-10(-7) M) was obtained, and the LTD4-induced contractions were expressed as the percent of the contraction evoked by 10(-5) M of ACh. We measured the contractile response to LTD4 in the presence or absence of the TXA2 antagonist, BAY u3405 (10(-8) M-10(-6) M). In the tracheal strips, BAY u3405 had no effect on the LTD4-induced contraction. However, in parenchymal strips, BAY u3405 significantly suppressed the contractile response to LTD4. These results suggest that in the central airway LTD4 contracts smooth muscle directly, but that in the peripheral airway LTD4 induces smooth muscle contraction both directly and indirectly, via TXA2.

Animals↗
PubMed1996

Cultured epithelial cells release cyclooxygenase-dependent and cyclooxygenase-independent factors that inhibit cholinergic contraction of canine airway smooth muscles.

We observed the effects of supernatants from cultured epithelial cells on the contraction of tracheal smooth muscle evoked by acetylcholine (ACh) or by electrical field stimulation (EFS). Cultured canine tracheal epithelial cells were incubated in Krebs solution with or without indomethacin (10(-5)M) for 30 and 120 min. The amplitude of the tracheal smooth muscle contractions evoked by EFS or exogenously applied ACh were measured before and after the application of each supernatant in the combined presence of both indomethacin (10(-5)M) and propranolol (10(-6)M). The control supernatant incubated without indomethacin markedly suppressed the amplitude of the contraction evoked by EFS, but not by ACh. The supernatant incubated with indomethacin for 30 min did not show any effects on the contractile responses evoked by EFS or ACh. However, the supernatants from the cultured epithelial cells incubated for a longer period (120 min) in the presence of indomethacin significantly suppressed the contraction evoked by EFS, but not by ACh. The prostaglandin E2 (PGE2) concentration was markedly higher in the supernatants incubated without indomethacin (1.39 +/- 0.51 ng/ml, 30 min incubation) than in those with indomethacin (0.02 +/- 0.01 ng/ml, 30 min incubation, and 0.06 +/- 0.01 ng/ml, 120 min incubation). To determine whether PGE2 is responsible for the inhibitory effect of the supernatants, we evaluated the effects of PGE2 on the resting tone, and EFS- or ACh-evoked contraction. 10(-12) to 10(-6) M of PGE2 showed no significant effect on the resting tone. 10(-9) M of PGE2, corresponding to the concentration of the supernatants incubated without indomethacin, and 10(-11) M of PGE2, to that of the supernatants incubated with indomethacin, showed a similar extent of inhibitory effects to the corresponding supernatants on the EFS-evoked contraction, and no effect on the ACh-evoked contraction. These results suggest that cultured airway epithelial cells release at least two factors spontaneously even without stimulation. One of these factors may be prostanoid (PGE2), which acts prejunctionally to inhibit the contractile response. The other factor is distinct from prostanoid and inhibits smooth muscle contraction, presumably by suppressing ACh release from vagus nerve termini.

Acetylcholine↗
PubMed1995

Ozone exposure suppresses epithelium-dependent relaxation in feline airway.

We examined the effect of exposure to ozone on the epithelium-dependent relaxation (EpDR) of bronchioles evoked by electrical field stimulation (EFS) in a feline model with hyperresponsive airways induced by exposure to ozone. Airway responsiveness was assessed by measuring the increases in total pulmonary resistance (RL) produced by aerosolized acetylcholine (ACh) in vivo. Airway responsiveness was also measured in vitro in dissected bronchiolar ring preparations. Exposure to ozone (3 ppm, 2h) significantly increased the airway responsiveness in vivo. The concentration of ACh required increasing RL to 200% of the baseline value, decreased from 1.97 mg/ml (GSEM 1.94) to 0.12 mg/ml (GSEM 1.77, p < 0.01) after exposure to ozone. EFS evoked atropine-, guanethidine-, and tetrodotoxin-resistant relaxations in the control bronchiolar rings precontracted by 5-hydroxytryptamine. Such relaxation was significantly suppressed by the mechanical denudation of epithelium, confirming that it was epithelium dependent. The amplitude of the EpDR was significantly suppressed in the animals exposed to ozone. These results suggest that EpDR is present in cats, and that its inhibition may contribute to the development of airway hyperresponsiveness.

Acetylcholine↗
PubMed1995

Effect of BAY u3405, a thromboxane A2 receptor antagonist, on neuro-effector transmission in canine tracheal tissue.

Thromboxane A2 (TXA2) is reported to potentiate vagal nerve neuro-effector transmission in airway smooth muscle tissue. We investigated the effects of BAY u3405 (3(R)-[[4-fluorophenyl)sulfonyl]amino]-1,2,3,4,-tetrahydro-9H-carbazole - 9-propanoic acid), a potent and selective TXA2 receptor antagonist, on the increase in vagal nerve neuro-effector transmission induced by a TXA2 mimetic, U-46619, in the canine trachea. We measured the contractions of canine tracheal smooth muscle evoked by electrical field stimulation (EFS) and by acetylcholine (ACh) in the presence and absence of a subthreshold dose of U-46619 (the highest dose that did not induce any smooth muscle contraction). We then examined whether BAY u3405 inhibited the effect of U-46619 on tracheal smooth muscle. The following results were obtained: (i) subthreshold doses of U-46619 (10(-10) M and 10(-9) M) significantly increased the amplitude of the contractions evoked by EFS; (ii) by contrast, U-46619 had no effect on the contractile response of smooth muscle to exogenously applied ACh; (iii) the contraction evoked by EFS was completely abolished by the application of atropine (10(-6) M) or tetrodotoxin (10(-7) M), indicating that EFS caused the smooth muscle contraction through the release of ACh from vagal nerve terminals; and (iv) pretreatment with BAY u3405 (10(-6) M) abolished the excitatory action of U-46619 on the amplitude of twitch contraction evoked by EFS in the trachea. These results indicate that U-46619, at low concentrations, has a prejunctional action stimulating neuro-effector transmission, presumably increasing ACh release from vagal nerve terminals through TXA2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

An important role of tachykinins in ozone-induced airway hyperresponsiveness.

We investigated the role of tachykinins in ozone-induced airway hyperresponsiveness (AHR) in guinea pigs. Airway responsiveness was assessed by determining the provocative concentration (PC200) of a histamine aerosol. Ozone exposure (3.0 ppm for 2 h) caused significant AHR. For vehicle-pretreated animals, the geometric mean pre- and post-ozone PC200 values were 0.87 mg/ml (GSEM 1.33) and 0.11 mg/ml (GSEM 1.17), respectively. Tachykinin depletion by capsaicin (50 mg/kg) prevented this AHR, whereas it did not alter pre-ozone airway responsiveness. The PC200 was 0.36 mg/kg (GSEM 1.64) before ozone and 0.24 mg/kg (GSEM 1.72) after ozone for this group. Ozone also caused a significant increase in neutrophils in bronchoalveolar lavage fluid (BALF) compared with BALF from a normal control group (1.71 +/- 0.69 versus 0.07 +/- 0.02 x 10(5)/ml, respectively). Capsaicin pretreatment attenuated this neutrophil influx (0.23 +/- 0.16 x 10(5)/ml). Morphometric assessment revealed edema of the bronchiolar wall after ozone exposure, which was not observed in the capsaicin group. BAL and morphometry revealed that the degree of ozone-induced epithelial desquamation was similar in both groups. These results suggest that tachykinins may be responsible for ozone-induced AHR, possibly via neurogenic inflammation.

Animals↗
PubMed1995

[A case of post-traumatic arteriovenous fistula of the subclavian artery].

A 67-year-old woman was admitted to our hospital for a complete medical evaluation of a pulmonary nodule on a chest X-ray film, which was found during an annual check-up. A loud bruit was audible over the left chest and the supraclavicular region. Computerized tomography (CT) scan and magnetic resonance imaging revealed an arteriovenous fistula from a branch of the left subclavian artery into the paravertebral veins. Angiography disclosed that the arteriovenous fistula was fed by the left costocervical artery. Transarterial embolization of the arteriovenous fistula was done with 5 mechanical detachable coils and 2 micro coils. Postembolization angiography showed a marked decrease in blood flow and near-elimination of the arteriovenous fistula. The shrinkage of the arteriovenous fistula was also observed on CT scan. This patient had been in a traffic accident, and had been clinically well before the accident. Post-traumatic arteriovenous fistula was strongly suspected, because a pulmonary nodule on chest X-ray film and a bruit were found after a traffic accident.

Accidents, Traffic↗
PubMed1994

Ipratropium bromide protects against bronchoconstriction during bronchoscopy.

Pulmonary function is reportedly impaired by fiberoptic bronchoscopy. We investigated the effect of two anticholinergic agents, intramuscular atropine and inhaled ipratropium bromide, on bronchoconstriction in 29 patients who were undergoing diagnostic bronchoscopy. The patients were divided into three groups; the first received 0.5 mg of atropine intramuscularly; the second took four puffs of 0.02 mg ipratropium bromide aerosolized by a metered-dose inhaler, and the third inhaled four puffs of a placebo. Fifteen minutes later a standardized topical anesthetic, lidocaine, was administered, and a bronchoscopic examination was performed. Pulmonary function was measured before and 15 minutes after each step. Pulmonary function was not affected by the treatment with anticholinergics or the placebo. In the placebo and the atropine groups, the topical anesthesia produced significant reductions in forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR); further reductions in these values were observed after bronchoscopy. In the group treated with ipratropium bromide there were no significant changes in FEV1 and PEFR after topical anesthesia. Bronchoscopy induced significant reductions in FEV1 and PEFR, but the changes were significantly smaller than those seen in the placebo and atropine groups. The results suggest that the deleterious effect of bronchoscopy on pulmonary function is due to topical lidocaine anesthesia and to the bronchoscopic examination itself. Inhaled ipratropium bromide protects against these deleterious effects, whereas intramuscular atropine does not.

Administration, Inhalation↗
PubMed1994

Airway epithelial cells modulate cholinergic neurotransmission in dog trachea.

We investigated the effects of epithelial cells on excitatory cholinergic neurotransmission in dog trachea, to shed more light on the role of airway epithelial cells in regulating airway responsiveness. Airway epithelial cells were prepared by an enzymatic dissociation of the tracheal mucosa using protease-free collagenase. Tracheal smooth muscle contractions evoked by electrical field stimulation (EFS) or acetylcholine (ACh) were measured before and after the application of epithelial cells. Isolated and dispersed epithelial cells (3 x 10(5) cells/ml) suppressed the amplitude of the twitch-like contractions evoked by EFS in the combined presence of guanethidine sulfate (10(-6) M) and indomethacin (10(-5) M). In contrast, epithelial cells did not affect the contraction evoked by exogenously applied ACh. Atropine (10(-6) M) or tetrodotoxin (10(-7) M) abolished the contraction evoked by electrical field stimulation. These findings indicate that airway epithelial cells inhibit the excitatory neurotransmission of the vagus nerve, presumably by suppressing the release of ACh. Airway epithelial cells may therefore play an important role in regulating the response of smooth muscle.

Acetylcholine↗
PubMed1994

VIP antagonists enhance excitatory cholinergic neurotransmission in the human airway.

It has been reported that a low concentration of exogenously applied vasoactive intestinal peptide (VIP) suppresses the release of acetylcholine (ACh) from vagus nerve terminals in the ferret and feline trachea. There has been, however, no documentation of the prejunctional action of VIP in the human airway. We observed the effects of VIP and VIP antagonists on cholinergic excitatory neuro-effector transmission in the human bronchus to study the possible role of endogenous VIP on excitatory neurotransmission. In the human bronchus, VIP (10(-10) to 10(-7) M) showed no effect on either the contractions evoked by electrical field stimulation (EPS) or those evoked by ACh. To investigate the possible role of endogenous VIP on the human bronchus, we observed the effects of the VIP antagonists [4-Cl-D-Phe6,Leu17]-VIP and [Ac-Tyr1,D-Phe2]-GRF(1-29)-NH2 on excitatory neuro-effector transmission. Both VIP antagonists (10(-8) M) significantly enhances the contractions evoked by EFS without affecting the ACh sensitivity of smooth muscle cells. These results indicate that VIP antagonists have a prejunctional action that enhances excitatory neurotransmission. This study suggests that endogenous VIP may suppresses ACh release from the vagus nerve terminals in the human airway. It is also suggested that exogenously applied VIP may be inactivated by some mechanism in the human airway.

Acetylcholine↗