Pharmacologic Effects of Grain Weevil Extract on Isolated Guinea Pig Tracheal Smooth Muscle

The grain weevil, an insect (pest) that infects grain, is a frequent contaminant of processed wheat, and its presence may contribute to respiratory abnormalities in grain workers. We studied the in vitro effects of an extract of grain weevil (GWE) on airway smooth muscle. Pharmacologic studies included in vitro challenge of guinea pig trachea with GWE, in parallel organ baths, pretreated with mediator-modifying agents or a control solution. Dose-related contractions of nonsensitized guinea pig trachea (GPT) were demonstrated using this extract. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth muscle contraction: atropine, indomethacin, pyrilamine, acivicin, NDGA, BPB, TMB8, captopril, and capsaicin. Atropine, pyrilamine, BPB, and capsaicin significantly reduced the contractile effects of the extract at most of the challenge doses (p < 0.01 or p < 0.05). Inhibition of GWE-induced contraction by blocking of other mediators was less complete. We suggest that GWE causes dose-related airway smooth muscle constriction of the GPT by nonimmunologic mechanisms involving a variety of airway mediators and possibly cholinergic receptors.     

Lung Tissue Resistance Measured in Saline-Filled Guinea Pig Lungs by Micropuncture

Lung tissue resistance (R_ti) measured in air-filled guinea pig lungs by the alveolar capsule technique was a large part of total lung resistance (R_l), and we wondered whether similar results applied to saline-filled lungs. We used the micropuncture method to measure alveolar pressure (P_alv) in saline-filled lungs of 21 guinea pigs. P_alv and airway opening pressure (P_ao) were measured before and after a sudden interruption of flow during an inflation or deflation maneuver. On stopping flow, there was an immediate large change in P_ao followed by a smaller slower change in P_ao. P_alv was nearly constant immediately after flow interruption but followed the slower change in P_ao. The initial change in P_ao on flow interruption was interpreted as the resistive pressure loss in the airways. The small change in P_ao and P_alv was interpreted as the pressure loss caused by tissue stress adaptation. Airway resistance (R_aw) and R_ti were obtained by dividing the pressure losses by the flow before the interruption. R_l was the sum of R_aw and R_ti. The calcium blocker nifedipine reduced both R_aw and R_ti and abolished the difference in R_ti between inflation and deflation. Values of R_ti were 10–29% of R_l. However, with correction for viscosity, R_ti predicted in air-filled lungs would dominate R_l. Accepted for publication: 21 February 1997     

Guinea Pig Pulmonary Mechanics: Altered Sensitivity to Carbachol by Cadmium and/or Selenium

Male Hartley guinea pigs (480–610 g) were treated intratracheally as follows: saline, cadmium (Cd, 0.3 mg), selenium (Se, 0.3 or 0.06 mg), or Se (0.06 mg) and Cd (0.3 mg) simultaneously. Selenium and Cd were administered as sodium selenite and cadmium chloride, respectively. Twenty-four h later, dynamic lung compliance (C_dyn) and pulmonary resistance (R_p) were measured before (baseline C_dyn and R_p) and after carbachol administration (0.0001, 0.001, 0.01, and 0.1 μmol/kg, intravenously). Results indicated a significant decrease in baseline C_dyn caused by 0.3 mg of Cd, 0.3 mg or 0.06 mg of Se, and 0.3 mg of Cd with 0.06 mg of Se (p < 0.05). A significant increase in baseline R_p due to 0.3 mg of Se was observed (p < 0.05). Carbachol decreased C_dyn significantly below baseline, evident after lower doses of carbachol, in guinea pigs pretreated with 0.3 mg of Se, whereas a significant improvement in C_dyn was seen after 0.0001 μmol/kg carbachol in the group pretreated with Se and Cd simultaneously (p < 0.05) compared with the respective baseline values of the saline-treated group. Similarly, a significant increase in R_p was observed after carbachol in groups pretreated with 0.3 mg of Cd or Se (p < 0.05). Results also indicated a significant increase in large airway constriction caused by Cd and/or Se (p < 0.05). A leftward shift in the carbachol dose-response curve indicated increased sensitivity to carbachol in Cd- and/or Se-pretreated guinea pigs. Accepted for publication: 14 March 1997     

Mediators and Oxygen Radicals in Hyperpnea-Induced Airway Constriction of Guinea Pigs

Leukotrienes (LTs), tachykinins (TKs), and oxygen radicals have been suggested to be important modulating factors for the hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. In this study, we tested the hypothesis that LTs and oxygen radicals modulate HIB by triggering TK release. Eighty-five Hartley guinea pigs were divided into four groups: control, dimethylthiourea (DMTU), FPL 55712, and A63162. DMTU is the scavenger for hydroxyl radical. FPL 55712 is an antagonist of LT receptor, whereas A63162 is an inhibitor of lipoxygenase. Each group was further divided into three subgroups: baseline, hyperpnea, and recovery. Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. We measured dynamic respiratory compliance (Crs), maximal expiratory flow at 50% total lung capacity (V_max50), and forced expiratory volume in 0.1 s (FEV_0.1) during the baseline and recovery periods. Hyperpnea caused significant decreases in Crs, V_max50, and FEV_0.1, indicating HIB in the control group. Pretreatment with DMTU, FPL 5712, or A63162 attenuated HIB. Plasma substance P (SP) levels increased progressively during the experiment in all groups. However, both FPL 55712 and A63162, but not DMTU, significantly decreased SP levels. Similarly, lung malondialdehyde (MDA) contents increased progressively during the experiment in the control group. Neither FPL 55712 nor A63162 significantly affected the increase. On the contrary, DMTU significantly attenuated the increase in MDA during the recovery period. These results suggest that inhibition of LTs leads to suppression at SP levels and HIB, whereas DMTU attenuates HIB by means of other mechanisms. Accepted for publication: 25 April 2000     

Effects of Cholecystokinin and Cholinergic Receptor Blockade on Guinea Pig Pepsinogen Secretion

Although cholecystokinin (CCK) has been reported to stimulate pepsinogen secretion, this action has been poorly characterized. To assess the ability of CCK to regulate mammalian pepsinogen secretion, guinea pig fundic mucosa was incubated in Ussing chambers with CCK-8, carbamylcholine, and pentagastrin, and with cholinergic and CCK antagonists. CCK-8 stimulated pepsinogen secretion at 10^?10M, with an ED₅₀ of 10^?9M and maximally (26-fold over basal) at 10^?8M. Carbachol stimulated pepsinogen and acid secretion with an ED₅₀ of 3 × 10^?7 M and maximally at 10^?6 M. Pentagastrin (10^?9 M-10^?6 M) did not affect acid or pepsinogen secretion, whereas gastrin-I (10^?6M) stimulated acid secretion slightly but did not alter pepsinogen secretion. L364.718 (10^?5 M), a specific CCK peripheral receptor antagonist, abolished all pepsigogic effects of 3 × 10^?9 M CCK-8 without altering basal acid or pepsinogen secretion or mucosal electric characteristics. L364,718-treated tissues unresponsive to CCK-8 nevertheless secreted pepsinogen and acid in response to 3 × 10^?7 M carbachol identically to control carbachol-treated preparations. Atropine (10^?5M) blocked the response to 3 × 10^?7M carbachol without inhibiting 10^?9M CCK stimulation. These results support a specific receptor-mediated role for cholecystokinin in the physiologic regulation of guinea pig pepsinogen secretion.     

Byssinosis: Role of Polymer Length on the Effect of Tannin on the Airway β-Adrenergic Receptor

Tannin, isolated from cotton bracts and implicated in the pathogenesis of byssinosis, inhibits isoproterenol and forskolin-stimulated cAMP release from airway cells in part by decreasing cell surface β-adrenergic receptor number and uncoupling the β-adrenergic receptor from its stimulatory G-protein (G_s) and in part by inhibiting adenylyl cyclase activity. We have hypothesized that cotton tannin, because of its long polymer length, interacts with the hydrophobic binding pocket of the β-adrenergic receptor and alters β-adrenergic receptor binding and G_s coupling. In these studies, tannins of three different polymer lengths and molecular masses were isolated from cotton bracts using sequential Amicon ultrafiltration [molecular mass > 10,000 (YM10 retentate), 1,000–10,000 (YM10 filtrate), and 1,000–5,000 Da (YM2 retentate)]. The YM10 retentate (25 μg/ml) decreased chloride secretion (Jnet = 1.11 ± 0.28 (control) to 0.59 ± 0.18 μEq/cm²·h, p < 0.05, n= 6), decreased cell surface β-adrenergic receptor number (18.0 ± 1.8 (control) to 10.6 ± 0.9 fmol/mg protein, p < 0.02, n= 4), and inhibited forskolin-stimulated cAMP release (5,254 ± 1,290 (control) to 2,968 ± 620 pmol/mg protein, p < 0.01, n= 8). In contrast, neither the YM10 filtrate nor the YM2 retentate had any effect on net chloride secretion, β-adrenergic cell surface receptor number, or forskolin-stimulated cAMP release. We conclude that polymer length is essential for the effect of tannin on the β-adrenergic receptor and on adenylyl cyclase. Accepted for publication: 28 June 1998     

Effects of GABA-B Agonist Baclofen on Bronchial Hyperreactivity to Inhaled Histamine in Subjects with Cervical Spinal Cord Injury

Bronchial provocation studies performed in our research center have consistently demonstrated airway hyperresponsiveness to both inhaled methacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported that the airways of such subjects maintained on chronic baclofen (γ-aminobutyric acid) therapy were not hyperreactive to inhaled methacholine. In this study we determined whether baclofen also blocks the effects of the bronchoprovocative agent histamine in subjects with cervical SCI. Twenty-four male subjects with cervical SCI participated in this study; 14 were maintained on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized histamine until either a 20% fall in forced expiratory volume in 1 s (FEV₁) from baseline (defined as PC₂₀) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjects (78.5%) and 8 of the 10 control subjects (80%) responded (PC₂₀ < 8 mg/ml) to the histamine challenge. Mean PC₂₀ values among responders in the baclofen (PC₂₀= 2.91 ± 2.3) and control (PC₂₀= 2.18 ± 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on cholinergic pathways, our findings that baclofen blocks bronchoconstriction due to inhaled methacholine, but not that due to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity. Accepted for publication 21 January 1997     

Inhibition of Isoproterenol-Induced Tachycardia by Azimilide in the Isolated Perfused Guinea Pig Heart

The class III antiarrhythmic agent, azimilide, has been shown to inhibit dihydroalprenolol binding to the beta-adrenergic receptor of rat brain and heart in an in-vitro ligand-binding assay. Azimilide, was assessed for beta-adrenergic activity, either agonist or antagonist, in the isolated perfused guinea pig heart in comparison with class III reference agents and the class II agent, propranolol. Varying concentrations of compound (0.03–100 M) were retrogradely perfused and the effects on corrected QT interval, baseline heart rate, and isoproterenol-stimulated heart rate were measured. Propranolol, dl-sotalol, azimilide, and d-sotalol inhibited isoproterenol-induced tachycardia with IC50 values (the concentration giving 50% inhibition of isoproterenol-stimulated heart rate) of 0.12, 1.4, 14.6, and 38.0 M, respectively. Clofilium, dofetilide, and sematilide did not affect the action of isoproterenol. Dofetilide, clofilium, azimilide, sematilide, dl-sotalol, and d-sotalol increased the QTc interval approximately 20 ms at concentrations of 0.1, 0.3, 1.0, 3.0, 30.0, and 100.0 M, respectively. The class III antiarrhythmic agents also slowed baseline heart rate and exhibited linear R-R and QT-interval relationships of similar slope. Azimilides antagonism of isoproterenol in this isolated heart model may reflect a direct receptor interaction or a contribution from the bradycardic action of the compound, which distinguishes it from several other pure I_Kr-blocking class III antiarrhythmic agents.     

The arterial site of action of nitric oxide in the neonatal pig lung determined by microfocal angiography

To determine the site of action of inhaled nitric oxide (iNO) in the newborn pig lung, lungs were isolated and perfused at constant flow for microfocal x-ray angiography. Measurements of pulmonary arterial diameters were made on arteries in the 100–2500 μm diameter range under control conditions, during vasoconstriction caused by hypoxia (decreasing PO₂ from ∼120 to ∼50 Torr), or N^ω-nitro-L-arginine methylester (L-NAME 10⁻⁴ M) administration, with or without vasodilation induced by iNO (40 ppm) or by the NO donor S-nitroso-N-acetylpenicillamine (SNAP 5 × 10⁻⁶ M) given intravascularly. Hypoxia caused constriction only in smaller arteries whereas L-NAME constricted arteries throughout the size range studied. iNO dilated the smaller arteries more than the larger arteries under all study conditions. SNAP was used to provide an intravascular source of NO for comparison to iNO. SNAP also dilated smaller arteries more than larger arteries, but it had a significantly greater effect on the large arteries than did iNO. This suggests that differential accessibility of the vascular smooth muscle to NO between sources, air and blood, is a factor in the diameter dependence of the responses. Accepted for publication: 13 March 2001     

Pharmacological Study of Oyster Mushroom (<Emphasis Type="Italic">Pleurotus Ostreatus</Emphasis>) Extract on Isolated Guinea Pig Trachea Smooth Muscle

Mushroom farm workers suffer from respiratory symptoms during the farming of mushrooms. The objective of this study was to analyze the effects of oyster mushroom (Pleurotus ostreatus) extract (OME) on isolated guinea pig tracheal smooth muscle in vitro. Isolated guinea pig tracheal tissue from 27 nonsensitized guinea pigs were studied. The OME was obtained from indoor mushroom growing fields and prepared as a 1:10 w/v aqueous solution. Dose-related contractions of nonsensitized guinea pig trachea were demonstrated using these extracts. The OME contained significant quantities of bacterial components (eg., endotoxin: 43,072.92 EU/mg). Parallel, pharmacological studies were performed by pre-treating the tissues with mediator-modifying agents including atropine, indomethacin, pyrilamine, BPB, acivicin, NDGA, captopril, TMB8 and capsaicin. Atropine consistently and strikingly reduced the contractile effects of this extract. These observations suggest an interaction of the OME with parasympathetic nerves or more directly with muscarinic receptors. Pretreatment with TMB8 (inhibitor of intracellular calcium mobilization) also significantly blocked the constrictor effect of OME, indicating a role of calcium mobilization in the constricting effect of OME. Inhibition of contraction by blocking of other mediators was less effective and varied depending on the drug. We conclude that OME causes a dose-related airway smooth muscle constriction by nonimmunological mechanisms involving a variety of airway mediators and possibly cholinergic receptors. This effect is not dependent on pre-sensitization of the guinea pigs.     

Variability of Airway Responses in Mice

We examined the effect of animal strain, type of spasmogen, and mode of spasmogen administration on the pattern of lung mechanical responses in intubated and mechanically ventilated mice. We determined the response in inspiratory respiratory system resistance (R_rs) and inspiratory static respiratory system compliance (C_rs) to increasing doses of inhaled or intravenous carbachol or serotonin in Balb/C and C57BL/6 mice. R_rs responsiveness was quantitated by calculating, by interpolation, the inhaled spasmogen concentration (PC₁₅₀) and intravenous spasmogen dose (PD₁₅₀) causing an increase in R_rs to 150% of baseline. C_rs responsiveness was calculated similarly for a decrease in C_rs to 85% of baseline (PC₈₅ for inhaled and PD₈₅ for intravenous spasmogen). Baseline R_rs and C_rs were similar in all groups. R_rs responsiveness to inhaled and intravenous carbachol and serotonin tended to plateau and was not different in the two strains. In contrast, C_rs responses were variable and had a greater mean PC₈₅ for inhaled serotonin than carbachol in both strains and a greater fall in mean C_rs at PC₁₅₀ for carbachol in Balb/C mice; no interstrain and interdrug differences in PD₈₅ were noted for intravenous spasmogens. Intravenous atropine attenuated the R_rs response to high-dose inhaled and intravenous serotonin, suggesting the involvement of a vagal reflex. In contrast, atropine attenuated C_rs responses only for intravenous serotonin in Balb/C mice. These results suggest that animal strain, spasmogen, and mode of administration determine the extent to which induced airflow resistance is accompanied by increases in elastic recoil. Accepted for publication: 24 June 1999     

Short Term Effects of Bracing on Exercise Performance in Mild Idiopathic Thoracic Scoliosis

In adolescent idiopathic thoracic scoliosis (ITS) working capacity may be reduced during exercise. Despite concern about its usefulness, bracing is still being used in ITS. Thus the effects of bracing on exercise performance need to be examined. We studied six females, ages 12–15 years who had mild ITS (Cobb angle range 20–35°). Pulmonary volumes, maximal voluntary ventilation (MVV), breathing pattern, the lowest (most negative in sign) pleural pressure during sniff maneuver (Ppl_sn), and pleural pressure swings (Ppl_sw) were measured first. Then, Ppl_sw, O₂ uptake (Vo ₂), CO₂ output (Vco ₂), heart rate (HR) at rest and during progressive incremental exercise on a cycling ergometer (10 watts/min) were recorded. The exercise test was performed under control conditions without bracing (C) and after 7 days of bracing with the brace on (B). Dyspnea was measured by a modified Borg scale. At rest, bracing mildly affected total lung capacity and forced vital capacity (p <0.03 for both) but not breathing pattern, Ppl_sn, or Ppl_sw(%Ppl_sn), a measure of respiratory effort. Furthermore, bracing did not consistently affect maximum work rate (WR_max). In both B and C VO₂ was below (<70%) the predicted value, Ve was below (<45%) MVV, and HR reserve was <15 beats/min, indicating some cardiovascular deconditioning. On the other hand, respiratory frequency (Rf) increased more in B than in C (p < 0.03). In addition, Ppl_sw, Ppl_sw(%Ppl_sn), and Ppl_sw(%Pplsn)/Vt, an index of neuroventilatory dissociation (NVD) of the respiratory pump, were greater in B (p < 0.03 for all). At a similar work rate, the Borg rating score was greater with bracing on than off, and the difference (ΔBorg) tended to relate to concurrent changes in Ppl_sw(%Ppl_sn)/Vt (r ²= 0.71; p < 0.07). We conclude that bracing affects respiratory effort, NVD, and dyspnea score during progressive exercise. These effects are consistent with increased lung elastance. Diminished exercise tolerance in patients with mild ITS probably reflects impaired physical fitness but is not affected by bracing. Training programs proposed for this subset of patients to increase peripheral muscle performance might also consider NVD of the respiratory pump. Accepted for publication: 27 January 1997     

Molecular and Biological Characterization of a New Isolate of Guinea Pig Cytomegalovirus

Development of a vaccine against congenital infection with human cytomegalovirus is complicated by the issue of re-infection, with subsequent vertical transmission, in women with pre-conception immunity to the virus. The study of experimental therapeutic prevention of re-infection would ideally be undertaken in a small animal model, such as the guinea pig cytomegalovirus (GPCMV) model, prior to human clinical trials. However, the ability to model re-infection in the GPCMV model has been limited by availability of only one strain of virus, the 22122 strain, isolated in 1957. In this report, we describe the isolation of a new GPCMV strain, the CIDMTR strain. This strain demonstrated morphological characteristics of a typical Herpesvirinae by electron microscopy. Illumina and PacBio sequencing demonstrated a genome of 232,778 nt. Novel open reading frames ORFs not found in reference strain 22122 included an additional MHC Class I homolog near the right genome terminus. The CIDMTR strain was capable of dissemination in immune compromised guinea pigs, and was found to be capable of congenital transmission in GPCMV-immune dams previously infected with salivary gland‑adapted strain 22122 virus. The availability of a new GPCMV strain should facilitate study of re-infection in this small animal model.     

Involvement of Tachykinins in Endotoxin-Induced Airway Hyperresponsiveness

Inhaled endotoxin, lipopolysaccharide (LPS), has been shown to result in bronchial hyperresponsiveness (BHR) to endogenous bronchoconstrictive mediators such as histamine. To determine the role of sensory neuropeptides released from bronchopulmonary C-fibers in LPS-induced BHR, 24 guinea pigs were allocated randomly to the following four groups. Animals in Groups I and IV were challenged with intratracheal instillation of 100 μl of saline vehicle, and those in Groups II and III with 1 mg of LPS (Escherichia coli, 0111:B4) in 100 μl of saline. Groups III and IV also received a high dose capsaicin (HDC) treatment to deplete tachykinins from C-fibers 1–2 weeks prior to the experiment. Animals were anesthetized and paralyzed, and total lung resistance (R_L) and compliance (C_dyn) were measured continuously during the experiment. Dose responses of R_L and C_dyn to histamine (0–8 μg/kg, intravenously) and capsaicin (0–1.6 μg/kg, intravenously), a specific C-fiber stimulant, were obtained prior to and at 1, 2, and 3 h following LPS/saline vehicle challenge. At 2 h after LPS, ΔR_L caused by histamine (8 μg/kg) was significantly higher in Group II (1.145%) than that in Group I (280%; p < 0.05); similarly, ΔR_L caused by capsaicin (1.6 μg/kg) was also increased after LPS (Group I, 107%; Group II, 267%; p < 0.05). Although HDC treatment completely abolished the bronchomotor response to capsaicin in both Groups III and IV, it enhanced the LPS-induced BHR to histamine (8 μg/kg; Group III, 1.834%; p < 0.05). In conclusion, these results suggest that the role of tachykinins in LPS-induced BHR may be dependent upon the type and the route of administration of the bronchoactive substance studied. Accepted for publication: 13 December 1996     

Short Term vs Long Term Dexamethasone Treatment: Effects on Rat Diaphragm Structure and Function

The effects of dexamethasone treatment duration (2.5 vs 10 weeks) on diaphragm myosin heavy chain isoforms, fiber types, and contractile characteristics were studied in male rats. Compared with ad libitum-fed and pair-fed controls, dexamethasone significantly decreased body weight, costal diaphragm weight, and the relative expression of myosin heavy chain isoform MHC-2B. Compared with pair-fed controls, the effect on MHC-2B expression was greater after 10 weeks than after 2.5 weeks. Type I and type II costal diaphragm fiber atrophy occurred, and type II fiber atrophy was greater after 10 weeks. Costal diaphragm-specific forces were not affected significantly by dexamethasone, regardless of the treatment duration or control group comparison. Fatigue resistance indexes were increased significantly after long term treatment compared with pair-fed controls and after both short term and long term treatment compared with ad libitum-fed controls. In conclusion, the effects of dexamethasone on MHC isoform phenotype expression, fiber type costal diaphragm atrophy, and fatigue resistance were dependent on treatment duration, with greater effects after long term (10 weeks) treatment. Accepted for publication: 24 November 1997     

Effect of Frequency and Tidal Volume on Pleural Pressure in Rabbits during High Frequency Ventilation

Regional effects of the chest wall on airway pressure transmission were studied during high frequency ventilation in anesthetized rabbits. We measured airway pressure (Paw), esophageal pressure (Pes), and costal pleural pressure (Ppl) by a rib capsule and flow and volume with a calibrated pneumotachograph. Using a closed circuit, pressures and flow were measured at varying frequencies (2–80 Hz) and tidal volumes (2–20 ml). Mean Pes and Ppl increased with flow amplitude above 100–250 ml/s, whereas mean Paw decreased, consistent with air trapping. Paw, Pes, and Ppl amplitudes increased monotonically with flow amplitude except above 400–500 ml/s, where the Ppl amplitude decreased suddenly. The latter occurring simultaneously with a sudden fall in mean Paw indicated airway flow limitation in costal regions. Flow instabilities during flow limitation were consistent with the large increase in the phase difference between Paw and Ppl and its variability, with frequency. By contrast, the phase difference between Paw and Pes and its variability were relatively small. These differences in Pes from Ppl responses might be caused by a difference in the impedance of the airway-mediastinum pathway or a direct transmission of tracheal pressure oscillations to the esophagus. The former suggests that constraints offered by the mediastinum and rib cage resulted in nonuniform ventilation during high frequency ventilation. Accepted for publication: 14 July 1998     

关附甲素对单个心肌细胞钙通道和内向整流钾通道的阻断作用

用膜片钳全细胞记录法观察关附甲素（ＧＡ）对分离的单个豚鼠心室肌细胞Ｌ型钙通道电流（ＩＣａ－Ｌ）和内向整流钾电流（Ｉｋ１）的影响。结果表明：ＧＡ抑制ＩＣａ－Ｌ：８,４０μＭＧＡ使ＩＣａ－Ｌ最大峰值从１０２０．８±１９７．３ｐＡ分别降至５２３．０±１０１．８和４２９．６±１２０．０ｐＡ（ｎ＝５,Ｐ均＜０．０１）,抑制率分别为４８．８％和５７．９％,ＧＡ使ＩＣａ－Ｌ的电流－电压曲线上移,但不改变其激活、峰值和反转电位。ＧＡ对Ｉｋ１没有影响,不改变Ｉｋ１的电流－电压曲线形态,亦不改变细胞的静息膜电位。结果提示ＧＡ对Ｉｃａ－Ｌ的阻滞作用为其抗心律失常效应的离子基础之一。     

Lack of Correlation between Nonspecific Nasal and Bronchial Reactivity in Allergic Rhinitis Subjects

A link between allergic rhinitis and asthma has long been suspected, allergic rhinitis being considered a precursor of asthma. The hypothesis is that if such a link exists, then nonspecific nasal and bronchial reactivity are already correlated in acute rhinitis patients. To test for this correlation, we compared nonspecific nasal and bronchial reactivity in two groups of rhinitis subjects: 37 rhinitis pollinosis patients tested during the pollen season and 35 rhinitis pollinosis patients tested outside the pollen season. We also assessed how smoking affects this link. In each subject, allergy, nonspecific nasal, and nonspecific bronchial reactivity were tested, and smoking was categorized. We found no correlation between nonspecific nasal and bronchial reactivity in the two nonasthmatic rhinitis groups. During active allergic inflammation (pollinosis season) no shift toward a stronger link between upper and lower airways can be found compared with the latent period (out of pollinosis season). Unexpectedly, among smokers we found a significant relationship between nonspecific nasal and bronchial reactivity. Thus, there is not yet sufficient evidence for a straightforward link between nasal and bronchial hyperreactivity in nonasthmatic pollinosis rhinitis subjects. The development of asthma seems to be crucial for this link. Accepted for publication: 30 November 1998