Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice

Collins, Rachel A.; Gualano, Rosa C.; Zosky, Graeme R.; Atkins, Constance L.; Turner, D.J.; Colasurdo, Giuseppe N.; Sly, Peter D.

doi:10.1186/1465-9921-6-142

Cited by 31 publications

(24 citation statements)

References 69 publications

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“…In the mouse model of RSV infection, whole-body plethysmography has been used to measure airway resistance, and we have found that AHR to inhaled methacholine correlates with pulmonary resistance when measured with more invasive techniques (18,36,46). In our study, we found that antioxidant treatment attenuated RSV-induced AHR, possibly due to a reduction in cys-LT production.…”

Section: Discussionsupporting

confidence: 49%

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung Inflammation

Castro

Guerrero-Plata

Suarez-Real

et al. 2006

Am J Respir Crit Care Med

146

154

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Section: Discussionsupporting

confidence: 49%

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung Inflammation

Castro

Guerrero-Plata

Suarez-Real

et al. 2006

Am J Respir Crit Care Med

146

154

View full text Add to dashboard Cite

“…The assessment of lung function on anesthetized mice was performed using the flexiVent system (SCIREQ, Montreal, Canada; Refs. 6,38).…”

Section: Methodsmentioning

confidence: 99%

Deregulated Stat3 signaling dissociates pulmonary inflammation from emphysema in gp130 mutant mice

Ruwanpura

McLeod

Miller

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Interleukin (IL)-6 is a potent immunomodulatory cytokine that is associated with emphysema, a major component of chronic obstructive pulmonary disease (COPD). IL-6 signaling via the gp130 coreceptor is coupled to multiple signaling pathways, especially the latent transcription factor signal transducer and activator of transcription (Stat)3. However, the pathological role of endogenous gp130-dependent Stat3 activation in emphysema is ill defined. To elucidate the role of the IL-6/gp130/Stat3 signaling axis in the cellular and molecular pathogenesis of emphysema, we employed a genetic complementation strategy using emphysematous gp130F/F mice displaying hyperactivation of endogenous Stat3 that were interbred with mice to impede Stat3 activity. Resected human lung tissue from patients with COPD and COPD-free individuals was also evaluated by immunohistochemistry. Genetic reduction of Stat3 hyperactivity in gp130F/F: Stat3 −/+ mice prevented lung inflammation and excessive protease activity; however, emphysema still developed. In support of these findings, Stat3 activation levels in human lung tissue correlated with the extent of pulmonary inflammation but not airflow obstruction in COPD. Furthermore, COPD lung tissue displayed increased levels of IL-6 and apoptotic alveolar cells, supporting our previous observation that increased endogenous IL-6 expression in the lungs of gp130F/F mice contributes to emphysema by promoting alveolar cell apoptosis. Collectively, our data suggest that IL-6 promotes emphysema via upregulation of Stat3-independent apoptosis, whereas IL-6 induction of lung inflammation occurs via Stat3. We propose that while discrete targeting of Stat3 may alleviate pulmonary inflammation, global targeting of IL-6 potentially represents a therapeutically advantageous approach to combat COPD phenotypes where emphysema predominates.

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“…If necessary, additional doses of anesthetics were given as required. In addition, the breath rate was set above normal (120 breaths/min) to suppress spontaneous breathing when measuring respiratory mechanics (7,18). Rats were allowed to stabilize on the ventilator for 5 min before the measurements were taken.…”

Section: Animalsmentioning

confidence: 99%

Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure

Jaenisch

Hentschke

Quagliotto

et al. 2011

Journal of Applied Physiology

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Jaenisch RB, Hentschke VS, Quagliotto E, Cavinato PR, Schmeing LA, Xavier LL, Dal Lago P. Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure. J Appl Physiol 111: 1664 -1670, 2011. First published September 8, 2011 doi:10.1152/japplphysiol.01245.2010.-Respiratory muscle training (RMT) improves functional capacity in chronic heart-failure (HF) patients, but the basis for this improvement remains unclear. We evaluate the effects of RMT on the hemodynamic and autonomic function, arterial baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats were assigned to one of four groups: sedentary sham (n ϭ 8), trained sham (n ϭ 8), sedentary HF (n ϭ 8), or trained HF (n ϭ 8). Trained animals underwent a RMT protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas sedentary animals did not. In HF rats, RMT had significant effects on several parameters. It reduced left ventricular (LV) end-diastolic pressure (P Ͻ 0.01), increased LV systolic pressure (P Ͻ 0.01), and reduced right ventricular hypertrophy (P Ͻ 0.01) and pulmonary (P Ͻ 0.001) and hepatic (P Ͻ 0.001) congestion. It also decreased resting heart rate (HR; P Ͻ 0.05), indicating a decrease in the sympathetic and an increase in the vagal modulation of HR. There was also an increase in baroreflex gain (P Ͻ 0.05). The respiratory system resistance was reduced (P Ͻ 0.001), which was associated with the reduction in tissue resistance after RMT (P Ͻ 0.01). The respiratory system and tissue elastance (Est) were also reduced by RMT (P Ͻ 0.01 and P Ͻ 0.05, respectively). Additionally, the quasistatic Est was reduced after RMT (P Ͻ 0.01). These findings show that a 6-wk RMT protocol in HF rats promotes an improvement in hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and respiratory mechanics, all of which are benefits associated with improvements in cardiopulmonary interaction. myocardial infarction; cardiovascular control; diaphragm; cardiopulmonary interaction THE HALLMARK SYMPTOMS OF heart failure (HF) subsequent to myocardial infarction (MI) are dyspnea and early fatigue, leading to reduced exercise tolerance and functional capacity (1). Furthermore, after MI, the neurohumoral excitation, which initially helps to preserve the cardiac output of patients who have systolic dysfunction, becomes deleterious with the persistence of cardiac dysfunction (12). In HF, the neurohumoral excitation is characterized by sympathetic hyperactivity and the attenuation of parasympathetic activity (12), which is associated with blunted baroreflex sensitivity (BRS) (30). In this context, impaired short-term control of arterial pressure (AP) and decreased heart-rate variability (HRV) (30) have been associated with an increased risk of sudden death of cardiac origin (45) and postinfarct mortality, regardless of the ejection fraction or ventricular arrhythmias (30).Together with the cardiovascular alterations, changes in the r...

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Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice

Abstract: Background: To characterise the acute physiological and inflammatory changes induced by low-dose RSV infection in mice.

Cited by 31 publications

References 69 publications

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung Inflammation

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung Inflammation

Deregulated Stat3 signaling dissociates pulmonary inflammation from emphysema in gp130 mutant mice

Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure

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