Role of C fibers in physiological responses to ozone in rats

The purpose of this study was to evaluate the role of C fibers in airway responsiveness after exposure to ozone (O3) in rats. The role of C fibers in the decreases in heart rate (HR) and core body temperature (Tc) that occur after inhalation of O3 was also examined. Neonatal rats were treated with capsaicin (Cap) or the vehicle used to dissolve capsaicin (Veh). Cap has been shown to cause permanent destruction of C fibers. When they reached adulthood, conscious minimally restrained rats were exposed to 2 ppm O3 or to air for 3 h. Two hours after the cessation of exposure, rats were anesthetized and instrumented for the measurement of pulmonary mechanics and airway responsiveness to inhaled aerosolized methacholine. O3 had no effect on baseline pulmonary conductance (GL) in either Veh or Cap rats but did cause a decrease in dynamic compliance (Cdyn) in Cap rats (P < 0.05). In Cap rats, O3 exposure caused a marked increase in airway responsiveness; the doses of inhaled aerosolized methacholine required to decrease GL and Cdyn by 50% were 6.5-fold and 9.8-fold lower in O3-compared with air-exposed rats (P < 0.005). In contrast, in Veh rats, O3 did not alter responsiveness. During O3 exposure, there was a profound, almost 50%, decrease in HR as measured with implanted electrodes. A decrease in Tc (measured with a rectal probe) of approximately 2.5 degrees C also occurred during O3 exposure. There was no significant effect of Cap pretreatment on the magnitude of these O3-induced changes in HR and Tc. Our results are consistent with the hypothesis that C fibers act to inhibit the development of hyperresponsiveness elicited by O3 inhalation but do not contribute to O3-induced changes in HR or Tc.

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Role of tachykinins in airway responses to ozone in rats

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.2.442 ◽

1998 ◽

Vol 85 (2) ◽

pp. 442-450 ◽

Cited By ~ 15

Author(s):

Toru Takebayashi ◽

Joseph Abraham ◽

G. G. Krishna Murthy ◽

Craig Lilly ◽

Ian Rodger ◽

...

Keyword(s):

Minute Ventilation ◽

Airway Responsiveness ◽

Lung Damage ◽

Pulmonary Mechanics ◽

Protective Effects ◽

Sprague Dawley ◽

C Fibers ◽

Neurokinin 1 ◽

Airway Responses

Previous studies that used neonatal capsaicin (Cap) treatment to ablate C fibers indicate that C fibers act to inhibit lung damage and airway hyperresponsiveness after ozone (O3) exposure in rats. The purpose of this study was to determine 1) the role of tachykinins in these protective effects and 2) whether differences in minute ventilation (V˙e) during O3 exposure might account for the effect of Cap. In the first study, male Sprague-Dawley rats were exposed to 1 part/million O3or air for 3 h. Four hours later, a bronchoalveolar lavage (BAL) was performed or airway responsiveness was measured. Rats were treated with CP-99994 and SR-48968, selective neurokinin-1- and -2-receptor antagonists, respectively, or with vehicle (Veh). O3 caused an increase in the number of neutrophils recovered from BAL fluid in both the Veh-treated and tachykinin-receptor antagonist (TKRA)-treated rats, but the number of neutrophils was approximately twofold greater in the TKRA-treated rats. In contrast, TKRA treatment had no effect on baseline pulmonary mechanics or airway responsiveness. After O3 exposure, the number of neutrophils in BAL fluid was also greater in Cap- than in Veh-treated rats. O3 reducedV˙e in both Veh- and Cap-treated rats, but the response was greater (reduction of 44.7 ± 3.7 vs. 27.8 ± 6.8%) and occurred earlier (10 vs. 70 min) in Cap- than in Veh-treated rats ( P < 0.02). These results suggest that tachykinins mediate protective effects of C fibers against O3-induced lung inflammation. The results also indicate that the more pronounced effect of O3 on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O3 resulting from greaterV˙e.

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Evaluation of the mechanism of decreased airway responsiveness in lambs

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.2.727 ◽

1989 ◽

Vol 66 (2) ◽

pp. 727-731 ◽

Cited By ~ 4

Author(s):

A. Stecenko ◽

K. McNicol ◽

S. Polk

Keyword(s):

Dynamic Compliance ◽

Open Lung Biopsy ◽

Airway Responsiveness ◽

Lung Mechanics ◽

Saline Control ◽

Aerosol Delivery ◽

Adult Sheep ◽

Adrenergic Activity ◽

Residual Capacity

In this study we investigated three possible mechanisms for the decreased airway responsiveness (AR) found in young lambs. To evaluate aerosol delivery, 6 adult sheep (9 mo-3 yr old) and 12 lambs (4–8 wk old) were challenged with aerosol (aH) and intravenous histamine (ivH). Awake animals were intubated and studied in a plethysmograph, which measured dynamic compliance (Cdyn), resistance of the lung, and functional residual capacity. AR to histamine was measured by administration of increasing concentrations of histamine until a significant change in lung mechanics occurred or until the maximum dose of histamine was given. In all six adult sheep, the response to both aH and iVH was a decrease in Cdyn. In two lambs Cdyn was decreased with both aH and ivH, in five lambs with neither, in three lambs with aH only, and in two lambs with ivH only. To examine the role of beta-adrenergic activity in determining AR, six adult sheep and six lambs received ivH and on a separate day ivH with propranolol pretreatment (p + ivH). The median effective dose of histamine that caused a reduction in Cdyn to 65% of normal saline control (ED65Cdyn) for the adult sheep given ivH was 3.60 (range 0.23–4.85) and 0.70 (range 0.49–8.0) micrograms.kg-1.min-1 for p + ivH (P = NS). The median ED65Cdyn for the six lambs was 8.0 micrograms.kg-1.min-1 for both ivH alone and p + ivH. To evaluate the role of airway smooth muscle (SM), AR to aH was quantitated in six adult sheep and six lambs, and then an open-lung biopsy was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of endotoxin on airway responsiveness to aerosol histamine in sheep

Journal of Applied Physiology ◽

10.1152/jappl.1983.54.6.1463 ◽

1983 ◽

Vol 54 (6) ◽

pp. 1463-1468 ◽

Cited By ~ 39

Author(s):

A. A. Hutchison ◽

J. M. Hinson ◽

K. L. Brigham ◽

J. R. Snapper

Keyword(s):

Dynamic Compliance ◽

Airway Responsiveness ◽

Lymph Flow ◽

Lung Mechanics ◽

Whole Body ◽

Base Line ◽

Residual Capacity ◽

Induced Changes ◽

Lung Lymph ◽

Lung Lymph Flow

This study tested the hypothesis that in the awake sheep, airway responsiveness to aerosol histamine would be increased acutely by endotoxemia. Eleven sheep were chronically instrumented to allow for measurements of lung lymph flow, vascular pressures, and lung mechanics. Awake sheep were studied in a whole-body plethysmograph designed to measure dynamic compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC). Pulmonary responsiveness to aerosol histamine was assessed by giving five breaths of increasing concentrations of histamine (0.1–50 mg/ml) until Cdyn decreased to 65% (of control) or until 50 mg/ml of histamine had been given. Escherichia coli endotoxin (0.2–0.5 microgram/kg) was then infused, and at 5 h after endotoxemia pulmonary responsiveness to aerosol histamine was remeasured. After endotoxin, 9 of the 11 sheep exhibited decreased Cdyn at a lower concentration of histamine compared with the preendotoxin level (P less than 0.05). The mean of the log dose of histamine necessary to reduce Cdyn to 65% of control was 1.00 +/- 0.16 (SE) before endotoxin and 0.027 +/- 0.29 5 h after endotoxin; i.e., histamine responsiveness was increased. In the last 3 sheep studied, atropine (0.1 mg/kg iv) was given after the second aerosol histamine challenge, and a third dose-response curve was performed. Atropine did not return the endotoxin-induced increase in histamine responsiveness to base line. There was no correlation between the change in histamine responsiveness and the endotoxin-induced changes in Cdyn, FRC, RL, alveolar-arterial O2 difference, pulmonary arterial pressure, or lung lymph flow.

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Pulmonary responses to acute ozone exposure in fasted mice: effect of leptin administration

Journal of Applied Physiology ◽

10.1152/japplphysiol.00300.2006 ◽

2007 ◽

Vol 102 (1) ◽

pp. 149-156 ◽

Cited By ~ 18

Author(s):

Richard A. Johnston ◽

Todd A. Theman ◽

Raya D. Terry ◽

Erin S. Williams ◽

Stephanie A. Shore

Keyword(s):

Bronchoalveolar Lavage ◽

Continuous Infusion ◽

Pulmonary Inflammation ◽

Airway Responsiveness ◽

Ozone Exposure ◽

Pulmonary Mechanics ◽

Serum Leptin ◽

Mechanistic Basis ◽

Inflammatory Profile ◽

Induced Changes

Leptin is a satiety hormone that also has proinflammatory effects, including augmentation of ozone-induced pulmonary inflammation. The purpose of this study was to determine whether reductions in endogenous levels of leptin can attenuate pulmonary responses to ozone. To reduce serum leptin, we fasted mice overnight before ozone exposure. Fasting caused a marked reduction in serum leptin to approximately one-sixth the levels observed in fed mice, and continuous infusion of leptin via Alzet micro-osmotic pumps restored serum leptin to, but not above, fed levels. Ozone exposure (2 ppm for 3 h) caused a significant, ∼40% increase in pulmonary resistance ( P < 0.01) and increased airway responsiveness in fasted but not in fed mice. The increased effect of ozone on pulmonary mechanics and airway responsiveness in fasted mice was not observed when leptin was restored via continuous infusion. Ozone exposure caused pulmonary inflammation, as evident by increases in bronchoalveolar lavage cells, protein, and soluble tumor necrosis factor receptors. There was no effect of fasting status on ozone-induced changes in the bronchoalveolar lavage inflammatory profile, and leptin treatment did not alter these responses. Our results indicate that fasting augments ozone-induced changes in pulmonary mechanics and airway responsiveness in mice. These effects of fasting are the result of declines in serum leptin. The mechanistic basis for this protective effect of leptin in fasted mice remains to be determined but is not related to effects on ozone-induced inflammation.

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Paradoxical Increase of Insulin Sensitivity Despite Blunted Adipose Tissue Browning in Genetic Ablation of IRP1 (OR09-08-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz041.or09-08-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Mikyoung You ◽

Jin-Seon Yook ◽

Soonkyu Chung

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Iron Metabolism ◽

Core Body Temperature ◽

Serum Levels ◽

Genetic Ablation ◽

Ucp1 Expression ◽

Core Body ◽

Tissue Browning

Abstract Objectives Iron regulatory protein 1 (IRP1) plays a key regulator of cellular iron metabolism, systemic oxygen sensing, and erythropoiesis. Deletion of IRP1 leads to profound HIF2a-dependent abnormalities in erythropoiesis and iron metabolism. Previously, we demonstrated that modulation of adipose tissue iron metabolism is necessary for adipose tissue browning. However, the role of IRP1 in adipose tissue browning and its metabolic consequences are uncertain. This study aimed to investigate the role of IRP1 in regulating adipose tissue browning in a mouse model of genetic ablation of IPR1 (IRP1−/−). Methods The IRP1−/− mice and wildtype (WT) controls were kept either at room (25°C) or cold (6°C) temperature for 7 days. Adipose tissue browning was evaluated by UCP1 expression and prevalence of beige-like structure in inguinal fat. Thermogenic heat release captured by infrared camera and core body temperature was measured by a rectal thermometer. The modulation of iron metabolism was assessed by serum levels of ferritin, hematocrit, and erythropoietin levels by ELISA. To investigate the role of IRP1 on energy metabolism, IRP1−/− and WT controls were fed a high-fat diet (45%) for 14 weeks. Insulin sensitivity was determined by glucose and insulin tolerance test and HOMA-IR score. [3H]-2-deoxyglucose (DOG) was injected to determine the distribution of 3H-radioactivity was quantified. Results IRP1−/− mice dramatically increased serum levels of erythropoietin but decreased hepcidin. IRP1−/− developed polycythemia and reticulocytosis, which was not affected by cold exposure. IRP1−/− were completely blunted in cold-induced browning in the inguinal fat showing no changes in UCP1 and adipocyte morphology. Unexpectedly, IRP1−/− showed higher core body temperature and heat release than control independent of UCP1 expression. Chronic intake of HF diet paradoxically increased the insulin sensitivity regardless of obesity. 2-DOG distribution was significantly increased in red blood cells, suggesting that red blood cell-dependent energy expenditure significantly contributed to rapid glucose disposal. Conclusions Disruption of IRP1 blunted adipose tissue browning. The paradoxical rise in insulin sensitivity in IRP1−/− is likely due to red blood cells-mediated energy expenditure. Funding Sources None.

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Altered Responses to Cold Environment in Urocortin 1 and Corticotropin-Releasing Factor Deficient Mice

Physiology Journal ◽

10.1155/2013/185767 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Bayan Chaker ◽

Tareq A. Samra ◽

Nabanita S. Datta ◽

Abdul B. Abou-Samra

Keyword(s):

Protein Metabolism ◽

Core Body Temperature ◽

Corticotropin Releasing Factor ◽

Dexamethasone Treatment ◽

Male And Female ◽

Dramatic Decline ◽

Urocortin 1 ◽

Core Body ◽

Deficient Mice

We examined core body temperature (CBT) of urocortin 1 (UCN1) and corticotropin releasing factor (CRF) knockout (KO) mice exposed to 4°C for 2 h. UCN1KO mice showed higher average CBT during cold exposure as compared to WT. The CBT of male and female WT mice dropped significantly to 34.1 ± 2.4 and 34.9 ± 3.1 C at 4°C, respectively. In contrast, the CBT of male and female UCN1KO mice dropped only slightly after 2 h at 4°C to 36.8 ± 0.7 and 38.1 ± 0.5 C, respectively. WT female and male UCN1KO mice showed significant acclimatization to cold; however, female UCN1KO mice did not show such a significant acclimatization. CRFKO mice showed a dramatic decline in CBT from 38.2 ± 0.4 at 22°C to 26.1 ± 9.8 at 4°C for 2 h. The CRF/UCN1 double KO (dKO) mice dropped their CBT to 32.5 ± 4.0 after 2 h exposure to 4°C. Dexamethasone treatment prevented the decline in CBT of the CRFKO and the dKO mice. Taken together, the data suggest a novel role for UCN1 in thermoregulation. The role of CRF is likely secondary to adrenal glucocorticoids, which have an important regulatory role on carbohydrate, fat, and protein metabolism.

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The role of prostanoids in ozone-induced changes in airway responsiveness: receptor activation-specific prostanoid release

Environmental Toxicology and Pharmacology ◽

10.1016/s1382-6689(97)10063-1 ◽

1998 ◽

Vol 5 (1) ◽

pp. 69-78 ◽

Cited By ~ 1

Author(s):

Helena J.M van Hoof ◽

Freek J Zijlstra ◽

Hans-Peter Voss ◽

Corné J.A.M Tak ◽

Leendert van Bree ◽

...

Keyword(s):

Receptor Activation ◽

Airway Responsiveness ◽

Induced Changes

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Role of the Accurate Detection of Core Body Temperature in the Early Detection of Coronavirus

Studies in Big Data - Big Data Analytics and Artificial Intelligence Against COVID-19: Innovation Vision and Approach ◽

10.1007/978-3-030-55258-9_14 ◽

2020 ◽

pp. 227-243

Author(s):

Enas Selem ◽

Sherine M. Abd El-kader

Keyword(s):

Body Temperature ◽

Early Detection ◽

Core Body Temperature ◽

Accurate Detection ◽

Core Body

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Tachykinins mediate hypocapnia-induced bronchoconstriction in guinea pigs

Journal of Applied Physiology ◽

10.1152/jappl.1989.67.6.2454 ◽

1989 ◽

Vol 67 (6) ◽

pp. 2454-2460 ◽

Cited By ~ 21

Author(s):

A. M. Reynolds ◽

R. D. McEvoy

Keyword(s):

Guinea Pig ◽

Lung Volume ◽

Circulatory Arrest ◽

Dynamic Compliance ◽

Sensory Nerves ◽

Gas Mixture ◽

Afferent Nerves ◽

Induced Changes ◽

Prior Administration

The aim of this study was to determine whether hypocapnia causes bronchoconstriction by releasing tachykinins (TKs) from C-afferent nerves in airways. Hypocapnia-induced bronchoconstriction (HIBC) was induced in anesthetized vagotomized guina pigs by ventilating lungs with a heated humidified hypocapnic gas mixture for 15 min after sudden circulatory arrest. The intensity of bronchoconstriction was assessed by calculating changes in dynamic compliance and by measuring the relaxation lung volume at the completion of experiments. Visualization of the airways by tantalum bronchography showed constriction of segmental bronchi with relative sparing of more proximal airways. Hypocapnia-induced bronchoconstriction was prevented by prior administration of salbutamol aerosol. Three experimental interventions were used to investigate the role of TKs in HIBC: 1) repeated capsaicin injections to deplete airway sensory nerves of TKs, 2) treatment with phosphoramidon, an inhibitor of enkephalinase, the main enzyme responsible for TK inactivation, and 3) topical airway anesthesia. Capsaicin pretreatment markedly attenuated the hypocapnia-induced changes in dynamic compliance (P less than 0.0005) and relaxation lung volume (P less than 0.0002), whereas phosphoramidon augmented these changes (P less than 0.02, P less than 0.03, respectively). Topical anesthesia of airways with lignocaine postponed the onset of bronchoconstriction, whereas the longer-acting, more lipid-soluble local anesthetic, bupivacaine, almost completely prevented HIBC. We conclude that, in the guinea pig lung, HIBC is mediated by TKs that are released after the activation of bronchial axonal reflexes.

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