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Biomedical subjects

K Sekizawa

Publications and source records attributed to K Sekizawa.

At least 19 recordsLinked to original sources
PubMed1992

Evidence that an atypical beta-adrenoceptor mediates the prejunctional inhibition of non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

We investigated the effect of the putative beta 3 agonist BRL 35135 on non-adrenergic non-cholinergic (NANC) contractions in guinea-pig bronchial strips. BRL 35135 (10(-9) to 10(-6) M) did not alter the baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion without having a significant effect on the contraction induced by substance P (10(-6) M). BRL 35135 (10(-6) M) also reduced the contraction induced by capsaicin (10(-7) M). Likewise, BRL 37344 (10(-9) to 10(-6) M) reduced NANC contractions induced by EFS in a concentration-dependent fashion. While BRL 37344 up to concentrations of 10(-8) M did not alter the contraction induced by SP (10(-6) M), BRL 37344 (10(-8) M) significantly inhibited NANC contractions induced by EFS and capsaicin (10(-7) M), (P less than 0.01). The inhibitory effect of BRL 35135 (10(-6) M) on NANC contractions induced by EFS was not significantly altered by the non-selective beta-adrenoceptor antagonists, propranolol and pindolol (P greater than 0.10), by the beta 1-selective antagonists, atenolol and metoprolol (P greater than 0.20) (10(-8) to 10(-6) M), or by the alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5) M) (P greater than 0.50). These results suggest that beta 3 agonists exert a prejunctional inhibitory action on NANC contractions.

Animals↗
PubMed1992

Inhibitory actions of prostaglandin E1 on neurogenic plasma extravasation in rat airways.

To determine whether neurogenic inflammation can be inhibited by prostaglandin E1 (PGE1), that is suggested to have an inhibitory effect on neuropeptide release from airway sensory nerves, we examined plasma extravasation in the airways of anesthetized rats in vivo with Evans blue due as a marker. Neurogenic inflammation was produced by an i.v. injection of capsaicin (100 micrograms/kg) or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V for 1 min). Capsaicin injection significantly increased leakage of dye in the trachea and main bronchi. Similar increases in leakage were seen in the trachea and right bronchus on electrical stimulation of the right vagus nerve. PGE1 (1-1000 micrograms/kg) inhibited the leakage induced by capsaicin in the trachea and bronchi concentration dependently with complete inhibition at a concentration of 1000 micrograms/kg. Likewise, PGE1 (1000 micrograms/kg) significantly inhibited electrical stimulation-induced leakage in the trachea and right bronchus (P less than 0.01). I.v. substance P (SP; 1 microgram/kg) increased Evans blue dye extravasation in the same way as the leakage induced by capsaicin and electrical stimulation but PGE1 (1000 micrograms/kg) failed to inhibit SP-induced leakage in the trachea and main bronchi (P greater than 0.20). These results suggest that PGE1 inhibits neurogenic plasma leakage by presynaptic inhibition of the release of neuropeptides from sensory nerves.

Alprostadil↗
PubMed1992

Opsonized zymosan decreases cytoplasmic motility of alveolar macrophages in dogs.

To examine the mechanisms of changes in alveolar macrophage (AM) activities caused by phagocytic stimulus, we studied the effect of opsonized zymosan (OZ) on cytoplasmic motility (CM) of AM from dog lungs in vitro. Four days after the instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the lower lobe bronchus, AM were harvested by broncho-alveolar lavage. AM were adhered to the bottom of plastic vials (10(6) cells of AM per each vial). Remanent field strength (RFS) from the AM containing Fe3O4 particles was measured immediately after magnetization. RFS decreased with time due to particle rotation (relaxation), which is related to cytoplasmic motility of AM. OZ (1-500 micrograms) decreased lambda 0 (the relaxation rate for the first min) in a concentration-dependent fashion. Neither BW755C (10(-5) M), indomethacin (10(-6) M), leupeptin (10(-5) M), bestatin (10(-5) M), nor superoxide dismutase (1000 U/ml) inhibited OZ (500 micrograms)-induced inhibitory effects on lambda 0, suggesting that cyclooxygenase and lipoxygenase products, serine, thiol enzymes, aminopeptidase and superoxide anion wer not responsible for OZ-induced effects. OZ (500 micrograms) significantly increased the intracellular concentration of Ca2+ (P less than 0.01). Likewise, OZ (500 micrograms)-induced effects on lambda 0 of AM were significantly inhibited by replacement of the medium with a Ca2+ free solution (P less than 0.01). These results imply that opsonized zymosan inhibits cytoplasmic motility of AM via external calcium influx.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1992

Influence of lung volume history and increased surface forces on collateral resistance.

In order to investigate the major route for collateral ventilation, the influences of lung volume history and increased surface forces on collateral resistance (Rcoll) were studied in excised canine lower lobes. Measurements were made during inflation and deflation in two states, i.e. before (control) and after stiffening by large tidal ventilation raising peak recoil pressure (Ptp) by 8-10 cmH2O. Air flowed into a wedged segment via a double lumen catheter (Vcoll) keeping segmental pressure (PS) constant at 2 cmH2O as monitored through the other lumen, giving Rcoll = Ps/Vcoll. Rcoll vs lung volume (VL) showed little hysteresis, in sharp contrast to Rcoll vs Ptp (Rcoll higher during inflation). Thus, in each state, Gcoll (= 1/Rcoll) depended primarily on VL, but the stiffed state appeared to have permanently enlarged channels or recruited new ones. The relations between Gcoll and VL or Ptp somewhat resemble reported bronchial diameter behaviour. The ventilation process itself, rather than higher surface forces per se, appeared to distend collateral channels in the stiff lung. The results are consistent with the major component of Gcoll being located at the bronchiole level.

Airway Resistance↗
PubMed1992

Vitamin B12 improves cognitive disturbance in rodents fed a choline-deficient diet.

The effect of vitamin B12 on learning disturbance was tested in rats. Rats were fed a choline-enriched, choline-deficient, and choline-deficient diet with vitamin B12. Concentrations of acetylcholine in the brain were significantly lower in rats fed a choline-deficient diet than rats fed a choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. However, there was no significant difference of acetylcholine in the brain or in the passive avoidance learning between rats fed a choline-enriched and a choline-deficient with vitamin B12 diet. We, therefore, suggest that vitamin B12 potentiates learning in an acetylcholine-deprived brain.

Acetylcholine↗
PubMed1992

Vascular permeability and airway narrowing during late asthmatic response in dogs treated with Metopirone.

Recently, we have developed an animal model of late asthmatic response (LAR) by treating naturally sensitized dogs to Ascaris suum antigen with the cortisol-synthesizing inhibitor, Metopirone. By using this animal model, we examined the contribution of edema in the airway wall to the development of LAR. To study whether airway microvascular leakage is increased in association with LAR, we performed antigen challenge in dogs treated with Metopirone. We measured the amount of extravasated Evans blue (EB) dye from the esophagus, trachea, and large and small bronchi 8 hours after the antigen challenge in dogs demonstrating immediate asthmatic response alone (IAR) and in dogs demonstrating both IAR and LAR. Airway responses to A. suum antigen were assessed by changes in respiratory resistance measured with the force oscillation technique at 3 Hz. EB dye extravasation did not increase significantly from that of control in any tissues in IAR (P greater than 0.10), but in LAR, it increased significantly from that of control (p less than 0.01) and IAR (p less than 0.05) in large and small bronchi. Histologic assessment of vascular permeability revealed that Monastral blue-labeled leaking vessels were only in sections from LAR, and leaking vessels were limited to small vessels (10 to 25 microns) in the trachea, large (diameter, greater than 5 mm) and small bronchi (2 to 4 mm in diameter), and bronchiole. The permeability index defined as the ratio of area of small vessels labeled with Monastral blue to that of the total small vessels in the walls was highest in the small bronchi. LAR significantly increased submucosal thickness of the small bronchi (p less than 0.05) compared with that in IAR. Both EB dye extravasation and permeability index in large and small bronchi also significantly increased during IAR within 3 minutes after the antigen challenge (p less than 0.05), but IAR did not alter the submucosal thickness of the small bronchi. These results imply that the increase in vascular permeability and submucosal thickness, especially in small bronchi, may be an important factor in the pathogenesis of LAR.

Airway Obstruction↗
PubMed1992

The role of cyclic AMP in non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 7.22 +/- 0.12 M and maximum inhibition was 100 +/- 0.01%). However, forskolin (less than 1 microM) did not alter the contraction induced by substance P (SP, 1 microM). 3. Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions induced by EFS (100 +/- 0.01%) without significant effect on SP (1 microM)-induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect against either NANC or SP-induced contractions. 4. Both the beta 2-adrenoceptor agonist, procaterol (0.1 nM to 3 nM) and theophylline (100 nM to 1 mM) concentration-dependently reduced EFS-induced NANC contractions without significant effect on SP (1 microM)-induced contractions. 5. In contrast to forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim inhibited the EFS-induced contractions only at those concentrations that similarly reduced the contractions induced by SP (1 microM). 6. These results suggest that cyclic AMP may mediate pre-junctional inhibition of NANC contractions in guinea-pig bronchi.

Animals↗
PubMed1992

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.

Adult↗
PubMed1992

Capsaicin desensitization inhibits cigarette smoke-induced increase in cytoplasmic motility of alveolar macrophages in guinea pigs.

To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar macrophages (AM), we measured remanent field strength (RFS) in guinea pigs with and without systemic capsaicin pretreatment in vivo. Four days after instillation of 3 mg/kg ferrimagnetic particles (Fe3O4) into the trachea, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time because of particle rotation (relaxation), which is thought to be correlated to CM of AM. The initial relaxation curve was fitted to an exponential function. The relaxation rate (lambda 0) increased during cigarette smoke inhalation and returned to baseline values within 5 min, and with the inhalation of the smoke of as many as three cigarettes, peak lambda 0 increased in animals without capsaicin pretreatment. However, cigarette smoke decreased lambda 0 with an increased number of cigarettes in animals with capsaicin pretreatment. Injection of nicotine or acetylcholine increased respiratory resistance to a degree similar to that observed with cigarette smoke, but it did not change lambda 0. However, substance P (SP) increased lambda 0, and repeated administration of SP produced a significant tachyphylaxis in animals with and without capsaicin pretreatment in a fashion similar to that noted with cigarette smoke inhalation. Acrolein decreased lambda 0 in animals with and without capsaicin. Colchicine inhibited the cigarette smoke-induced increase in lambda 0.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Effective site of bronchodilation by beta-adrenergic and anticholinergic agents in patients with chronic obstructive pulmonary disease: direct measurement of intrabronchial pressure with a new catheter.

To study the effective site of bronchodilators in patients with chronic obstructive pulmonary disease (COPD), a catheter tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus, 3 mm inner diameter, in 14 patients with COPD. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (RP) was obtained by the subtraction of RC from RL. This technique permitted identification of the site of changes in airway resistance. Atropine sulfate (5 mg/ml) was continuously inhaled during tidal breathing for 1 min by seven patients (Group A), and the other seven patients (Group B) inhaled fenoterol (1 mg/ml) for 1 min. The doses that were actually delivered were 0.75 mg for atropine sulfate and 0.15 mg for fenoterol. The baseline resistances of RC and RP were 3.9 +/- 0.8 and 3.7 +/- 0.6 cm H2O/L/s in Group A, and 4.3 +/- 0.5 and 3.5 +/- 0.4 cm H2O/L/s in Group B, respectively. Both atropine sulfate and fenoterol significantly decreased RL by an average of 2.4 and 2.6 cm H2O/L/s, and there was no significant difference between them (p greater than 0.20). The percentage decrease in resistance from the baseline values by fenoterol did not differ significantly between RC and RP (p greater than 0.20). However, atropine sulfate significantly decreased RC more than RP.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1992

Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma.

To partition the central and peripheral airway resistance, a catheter-tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus with a 3 mm inner diameter in 10 patients with asymptomatic asthma. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by subtraction of RC from RL. Therefore, our measurement of Rp included lung tissue resistance. The technique permitted identification of the site of changes in airway resistance. The baseline values of resistances were 2.3 +/- 0.2 cm H2O/L/s in RL, 1.5 +/- 0.1 cm H2O/L/s in RC, and 0.8 +/- 0.1 cm H2O/L/s in Rp, respectively. To determine the site of airway hyperresponsiveness, dose-response curves of central, peripheral, and total airways to inhaled methacholine were separately constructed. Bronchial responsiveness was evaluated by a log methacholine unit requiring a 35% decrease (PC35) and a 50% decrease (PC50) in pulmonary conductance (a reciprocal of RL). We calculated the increase of resistances in total (delta RL), central (delta RC), and peripheral (delta Rp) airways from the baseline values at either PC35 or PC50.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Prevention of respiratory infections in elderly bed-bound nursing home patients.

A procedure to prevent silent aspiration, which results in frequent respiratory infections, was conducted on elderly bed-bound nursing home patients who suffered mainly from cerebral infarction and dementia. We cleaned the mouth with povidone iodine and kept them in a sitting position for 2 hr after each meal in order to restrict respiratory bacterial infection and to prevent aspiration of gastric juices, respectively. Patients with urinary tract infections were excluded from the present protocol. During the treatment for 103 days the number of febrile days was significantly decreased in the treated group compared with the control group, probably due to minimizing of respiratory infections.

Aged↗
PubMed1992

[Bactericidal clothes protect against respiratory infections in the elderly patients].

In order to protect against infections in the elderly patients, bactericidal clothes were used. Ninety elderly patients were divided into two groups; the control group and the other group with bactericidal clothes. In period I neither group received particular treatment for three months and in period II only the treated group used bactericidal clothes for three months. The control group in period II used regular clothes throughout. Cause of fever (greater than 37 degrees C) extending more than 10 or 15 days were significantly lower in the treated group than in the control group. It was suggested that the bactericidal clothes reduce infections in elderly patients.

Aged↗
PubMed1992

Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine.

The contractile response of isolated guinea pig trachea to histamine was potentiated in the presence of the histamine N-methyltransferase (HMT) inhibitor SKF 91488, whereas the diamine oxidase inhibitor aminoguanidine was without effect. SKF 91488 shifted in a concentration-dependent fashion the concentration-response curves to histamine to lower concentrations with the maximum by 1 log unit. The trachea contained significant HMT activity (45.4 +/- 5.0 pmol/min/mg protein). In situ hybridization to detect HMT mRNA indicated that HMT mRNA was present in the epithelium and endothelium, being more abundant in the former. Removal of the epithelium shifted the concentration-response curves to histamine to lower concentrations by 0.8 log unit, and SKF 91488 caused only a slight shift of histamine concentration-response curves in tissues denuded of epithelium. These findings suggest that HMT regulates the contractile response of guinea pig trachea to histamine, and epithelial removal-induced bronchial hyperresponsiveness to histamine is largely explained by the loss of HMT in the epithelium.

Animals↗
PubMed1991

Pre- and postjunctional muscarinic receptor subtypes in dog airways.

To examine muscarinic receptor subtypes involved in cholinergically mediated contractions of the airway, we studied the effects of the M1-selective antagonist, pirenzepine, the M2-selective antagonist, AF-DX 116, the M3-selective antagonist, 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP) methiodide, and the non-selective antagonist, atropine, on acetylcholine (ACh)- and electrically induced contractions in dog bronchi and bronchioles. The relative potencies of the antagonists based on IC50 values of each antagonist for contractions induced by the two concentrations of ACh that produced 50% of the maximum (ED50) and the maximum (EDmax) contractions and the pA2 values were atropine greater than or equal to 4-DAMP methiodide greater than pirenzepine = AF-DX 116 in both the bronchi and bronchioles. The IC50 and pA2 values of each antagonist did not differ significantly between the bronchi and bronchioles. 4-DAMP methiodide significantly inhibited the contractile response to electrical field stimulation (EFS) at 5 Hz at concentrations that did not alter the contractile responses to exogenous ACh in both the bronchi and bronchioles, whereas pirenzepine, AF-DX 116 and atropine inhibited the EFS-induced contraction only at the concentrations that reduced the contraction induced by exogenous ACh. The present results suggest that the cholinergic contraction is mediated via the postsynaptic receptor M3, based on functional potencies of muscarinic antagonists and presynaptic receptor auto-facilitatory M3, based on the suppression of the contractile response to EFS by 4-DAMP methiodide in central and peripheral airways.

Acetylcholine↗
PubMed1991

Nicotine improves cognitive disturbance in rodents fed with a choline-deficient diet.

The effect of nicotine on learning disturbances was tested in rats. Rats were fed either a choline-enriched or a choline-deficient diet. Concentration of acetylcholine in the whole brain was significantly lower in rats fed with choline-deficient diet than rats fed with choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. Nicotine (0.04 mg/kg) administered intraperitoneally significantly potentiated learning in rats on a choline-deficient diet, as well as in rats on a choline-enriched diet. We, therefore, suggest that nicotine may potentiate learning in an acetylcholine-deprived brain.

Acetylcholine↗