Oxygen radicals and substance P in perinatal hypoxia-exaggerated, monocrotaline-induced pulmonary hypertension.

Perinatal hypoxia has been observed to cause more aggressive pulmonary hypertension in human. Several mediators such as reactive oxygen species (ROS) and substance P are believed to be crucial in the mechanism of inducing pulmonary hypertension. This study was designed to test whether substance P and ROS play a role in perinatal hypoxia-exaggerated, monocrotaline (MCT)-induced pulmonary hypertension.

The role of mast cells in citric acid-induced airway constriction and cough.

Inhalation of citric acid (CA) causes airway constriction and coughing. To investigate the role of mast cells in CA-induced airway constriction and cough, three experiments using guinea pigs were carried out. In the first experiment, we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit synthesis of leukotrienes, pyrilamine to antagonize histamine H1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase.

Propofol attenuates the decrease of dynamic compliance and water content in the lung by decreasing oxidative radicals released from the reperfused liver.

Background: Remote pulmonary injuries after hepatic reperfusion are frequently caused by reactive oxygen species (ROS)-induced damage. The choice of anesthetics may affect the balance between oxidants and antioxidants, and propofol, a commonly used anesthetic, has an antioxidant effect. In this study, we developed a model to study pulmonary function with hepatic ischemia/reperfusion (I/R) manipulation, with the aim of defining remote pulmonary dysfunction after hepatic reperfusion and determining if propofol affects this dysfunction by altering ROS production from the liver or lungs.

Motorcycle exhaust particles augment antigen-induced airway inflammation in BALB/c mice.

Evidence indicates that environment pollutants from fossil fuel combustion compromise the immune system by enhancing allergic reactions and damaging the respiratory tract. This study was performed to investigate the effects of motorcycle exhaust particles (MEP), a major air pollutant especially in the urban areas of Taiwan, on allergen-induced airway inflammatory reactions in lab animals. BALB/c mice were intratracheally instilled with ovalbumin (OVA), MEP, or phosphate-buffered saline, 3 times every 2 wk.

End-expiratory and tidal volumes measured in conscious mice using single projection x-ray images.

The evaluation of airway resistance (R(aw)) in conscious mice requires both end-expiratory (V(e)) and tidal volumes (V(t)) (Lai-Fook SJ and Lai YL. J Appl Physiol 98: 2204-2218, 2005). In anesthetized BALB/c mice we measured lung area (A(L)) from ventral-to-dorsal x-ray images taken at FRC (V(e)) and after air inflation with 0.

Erythropoietin protects post-ischemic hearts by preventing extracellular matrix degradation: role of Jak2-ERK pathway.

Factors predisposing to extracellular matrix degradation associated with myocardial ischemia/reperfusion (IR) usually cause cell death. Recombinant human erythropoietin (EPO) protects the myocardium from IR, but whether it affects extracellular matrix (ECM) degradation is not known. This study examined the effect of the Jak2-ERK pathway, which is triggered by EPO, on the expression of matrix metalloproteinases (MMPs), tissue inhibitor of MMP 4 (TIMP-4), and collagen in post-ischemic hearts.

Mast cell mediators in citric acid-induced airway constriction of guinea pigs.

We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H1 receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA.

Detection of mediator-induced airway constriction by barometric plethysmography in mice.

The barometric method has recently been employed to detect airway constriction in small animals. This study was designed to evaluate the barometric method to detect mediator-induced central and peripheral airway constriction in BALB/c mice. First, the central airway constrictor carbachol and the peripheral airway constrictor histamine were employed to induce airway constriction, which was detected by both the conventional body plethysmography and the barometric method in anesthetized mice.

Airway resistance due to alveolar gas compression measured by barometric plethysmography in mice.

We developed a method for measuring airway resistance (R(aw)) in mice that does not require a measurement of airway flow. An analysis of R(aw) induced by alveolar gas compression showed the following relationship for an animal breathing spontaneously in a closed box: R(aw) = A(bt)V(b)/[V(t) (V(e) + 0.5V(t))].

Mast cells in citric acid-induced cough of guinea pigs.

It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H(1) receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase.

Nasal administration of albuterol: an alternative route of delivery.

The use of metered-dose inhalers for the delivery of albuterol, a beta2-selective adrenergic agonist, is associated with drawbacks, especially in children and the elderly. This investigation was designed to assess the effectiveness of albuterol delivered intranasally and to compare this delivery route with intratracheal and intravenous delivery. Three parameters of pulmonary function (peak maximal expiratory flow, maximal expiratory flow at 50% vital capacity, and total lung capacity) in anaesthetized, artificially ventilated guinea pigs were used to determine the degree of protection produced by albuterol against bronchoconstrictor responses provoked by acetylcholine.

Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs.

Fullerene derivatives have often been used as effective scavengers for reactive oxygen species (ROS). This study was designed to test whether polyhydroxylated fullerene derivatives [C(60)(OH)(7+/-2)] protect against oxidative stress in cultured RAW 264.7 cells and ischemia-reperfused (IR) lungs.

Mast cells and reactive oxygen species in citric acid-induced airway constriction.

The noncholinergic airway constriction is mediated by tachykinins, mainly neurokinin A and substance P, and this bronchoconstriction is usually enhanced during inflammatory episodes. We demonstrated previously that reactive oxygen species play an important role in capsaicin-, hyperventilation-, and citric acid (CA) inhalation-induced noncholinergic airway constriction. For understanding cellular involvement, we further investigated the relationship between mast cells, bradykinin (BK), reactive oxygen species, and noncholinergic airway constriction.

Chronic hypoxia- and monocrotaline-induced elevation of hypoxia-inducible factor-1 alpha levels and pulmonary hypertension.

A close relationship exists between hypoxia-inducible factor (HIF)-1alpha and pulmonary hypertension. The present study was carried out to explore if there are temporal alterations in HIF-1alpha levels during prolonged hypoxia and after monocrotaline (MCT) treatment. First, young Wistar rats were divided into 5 groups: control, hypoxia-1, hypoxia-2, hypoxia-3 and hypoxia-4.

Effectiveness of Dp2 nasal therapy for Dp2- induced airway inflammation in mice: using oral Ganoderma lucidum as an immunomodulator.

Nasal immunotherapy with allergen has been reported to be effective for airway allergic disease. A group of 50 male Balb/c mice were immunized intraperitoneally with recombinant Dermatophagoides pteronyssinus group 2 (rDp2), then oral feeding with Ganoderma lucidum (known as "Ling Zhi," LZ OT) and intranasal therapy with native Dp2 (Dp2 NT) were given, the mice then received intratracheal challenge with rDp2 at 28 days and 35 days after immunization. Airway hypersensitivity to methacholine was measured 30 min (early phase) and 24 h (late phase) after the second challenge.

Overexpression of placenta growth factor contributes to the pathogenesis of pulmonary emphysema.

To examine the role of placenta growth factor (PlGF) in the pathogenesis of pulmonary emphysema, we generated PlGF-transgenic (TG) mice using a phosphoglycerate kinase promoter. This resulted in constitutive overexpression of PlGF. In these TG mice, pulmonary emphysema, with enlarged air spaces and enhanced pulmonary compliance, first appeared at 6 months of age and became prominent at 12 months.

RNA interference prevents lipopolysaccharide-induced preprotachykinin gene expression.

We showed previously that lipopolysaccharide (LPS) induces noncholinergic airway hyperreactivity to capsaicin via an upregulation of tachykinin synthesis. This study was designed to test whether double-stranded preprotachykinin (ds PPT) RNA, RNA interference (RNAi), prevents the LPS-induced alterations. First, cultured primary nodose ganglial cells of newborn Brown-Norway rats were divided into four groups: control; LPS; LPS+RNAi; and LPS+RNAi+liposome.

Efficacy of local nasal immunotherapy for Dp2-induced airway inflammation in mice: Using Dp2 peptide and fungal immunomodulatory peptide.

Background: Local nasal immunotherapy (LNIT) is an effective immunotherapy. Peptides derived from the group 2 allergen of Dermatophagoides pteronyssinus, Dp2 28-40 and Dp2 28-40A, and fungal immunomodulatory peptide (FIP) have been shown to act as T(H)1 potential and response-inducing adjuvant. LNIT by the use of Dp2 peptides in conjunction with FIP were investigated.

Airway hyperresponsiveness and remodeling in antigen-challenged guinea pigs.

Airway hyperresponsiveness (AHR) is the main feature of allergic subjects/animals, and its underlying mechanism is not clear. We explored whether antigen-induced AHR is associated with cytokine generation, inflammatory cell infiltration, and/or remodeling of airway smooth muscle. Guinea pigs were divided into three groups: control-1, control-2, and ovalbumin (OA).

Lipopolysaccharide induces preprotachykinin gene expression.

This study was performed to test whether biosynthesis of tachykinins plays a pivotal role in lipopolysaccharide (LPS)-induced airway alteration by analyzing preprotachykinin-I (PPT-I, a precursor of tachykinins) gene expression. Brown-Norway rats (11-12 wk old) were divided into four groups: control; LPS; dimethylthiourea (DMTU, an effective hydroxyl radical scavenger); and DMTU+LPS. Each animal in the control group received saline treatment.

Tachykinin dysfunction attenuates monocrotaline-induced pulmonary hypertension.

We explored the dysfunction of tachykinins on monocrotaline (MCT)-induced pulmonary hypertension by using double-stranded preprotachykinin (ds PPT) RNA and neurokinin receptor (NK) antagonists. Here, we showed the possibility to attenuate the PPT gene expression by ds RNA, RNA interference (RNAi), in fully developed tissue of rats. We designed four groups (control, MCT, RNAi + MCT, and solvent + MCT) of experiments in series 1 and seven groups (control, MCT, MCT + CP-96345-3.

Reactive oxygen species in sustained airway constriction induced by citric acid aerosol inhalation.

We tested if there is a direct relationship between reactive oxygen species and citric acid-induced airway constriction. Guinea pigs were divided into two groups: control and dimethylthiourea (a hydroxyl radical scavenger). The animals in each group were further separated into four subgroups: baseline, recovery 2-3 min, recovery 10 min, and recovery 20 min.

Hyperpnea-induced production of TBHP-initiated chemiluminescence in guinea pigs.

Antioxidants attenuate hyperpnea-induced airway constriction. It was hypothesized that this type of airway constriction is closely related to reactive oxygen species (ROS). However, there is no direct evidence of an increase in ROS during or right after the course of hyperpnea.

Temporal increase in the reactivity of pulmonary vasculature to substance P in chronically hypoxic rats.

We previously demonstrated that the pulmonary vascular response to substance P (SP) increased in chronically hypoxic rats. This study explored the temporal increase in reactivity of the pulmonary vascular response to SP and its underlying mechanisms. First, young female Wistar rats were exposed to sea level (SL) or simulated high altitude (HA) for 15 h/day for 3 days, 1 wk, 2 wk, and 4 wk.