thiourea and Hyperventilation

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. To detect ROS production induced by hyperpnea, forty one guinea pigs were divided into four groups: control; control with 95% O2-5% CO2; hyperpnea with 95% air-5% CO2; and hyperpnea with 95% O2-5% CO2. Three minutes following hyperpnea or at the equivalent time, we obtained bronchoalveolar lavage (BAL) and measured its chemiluminescence (CL) counts. In addition, hyperpnea with 95% O2-5% CO2 gas mixture was carried out and BAL was collected 3 minutes after the hyperpnea in an additional forty animals. We measured CL counts in BAL samples before and after the treatments of the following ROS scavenger(s) or saline in vitro: control (saline); superoxide dismutase (SOD); catalase; dimethylthiourea (DMTU); and SOD+catalase+DMTU. Hyperpnea with 95% O2-5% CO2, but not with 95% air-5% CO2, gas mixture induced significant increase in t-butyl hydroperoxide-initiated CL counts, which were inhibited by DMTU, catalase, or SOD in vitro. Our data suggest that hyperpnea with a 95% O2-5% CO2, but not with 95% air-5% CO2, gas mixture induced an increase in ROS production.

Topics: Animals; Bronchoalveolar Lavage Fluid; Catalase; Guinea Pigs; Hyperventilation; In Vitro Techniques; Luminescent Measurements; Reactive Oxygen Species; Superoxide Dismutase; tert-Butylhydroperoxide; Thiourea

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(max(50))), and forced expiratory volume in 0.1 s (FEV(0.1)) during the baseline and recovery periods. Hyperpnea caused significant decreases in Crs, V(max(50)), 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.

Topics: Acetamides; Animals; Bronchoconstriction; Chromones; Female; Free Radical Scavengers; Guinea Pigs; Hyperventilation; Leukotriene Antagonists; Leukotrienes; Lipoxygenase Inhibitors; Lung; Male; Malondialdehyde; Phenyl Ethers; Reactive Oxygen Species; Substance P; Tachykinins; Thiourea

1. The present authors recently found that a marked hyperpnoea-induced bronchoconstriction (HIB) only occurred in guinea-pigs after treatment with propranolol, a non-selective beta-adrenoceptor antagonist. This study investigated tachykinin-dependent and antioxidant-modulated mechanisms for this propranolol-augmented HIB. 2. Guinea-pigs were pre-treated with an antioxidant, dimethylthiourea (DMTU), or saline for 3 days. On the day of study, each animal was given a dose of propranolol (0.5 mg kg(-1)), then the airway function was examined in the anaesthetized-paralysed animal before, during and after hyperpnoea with a dry 95% O2:5% CO2 gas mixture. Tracheal neutral endopeptidase (NEP) activity and plasma substance P (SP) level were measured after functional study. 3. In the presence of propranolol, HIB was augmented, and was found to be associated with decreased NEP activity and an increased plasma SP level. The augmented HIB was attenuated by DMTU. 4. Therefore, the present results suggest that propranolol-augmented HIB is tachykinin-dependent and is modulated by DMTU.

Topics: Adrenergic beta-Antagonists; Animals; Blood Pressure; Bronchoconstriction; Free Radical Scavengers; Guinea Pigs; Heart Rate; Hyperventilation; Male; Neprilysin; Propranolol; Substance P; Tachykinins; Thiourea; Trachea