Commentary: Central-acting therapeutics alleviate respiratory weakness caused by heart failure–induced ventilatory overdrive
| العنوان: | Commentary: Central-acting therapeutics alleviate respiratory weakness caused by heart failure–induced ventilatory overdrive |
|---|---|
| المؤلفون: | Amy M. Pastva, Julia K. L. Walker |
| المصدر: | Frontiers in Physiology, Vol 9 (2018) Frontiers in Physiology |
| بيانات النشر: | Frontiers Media S.A., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Weakness, respiratory muscle weakness, Physiology, Diaphragm, Eukaryotic Initiation Factor-2, 030204 cardiovascular system & hematology, Blood–brain barrier, lcsh:Physiology, GPCR Signaling, Mice, 03 medical and health sciences, 0302 clinical medicine, GPCR signaling, Physiology (medical), Internal medicine, medicine, Animals, Respiratory muscle weakness, Phosphorylation, Respiratory system, Lung, ventilatory overdrive, Heart Failure, heterodimer receptor, Muscle Weakness, lcsh:QP1-981, General Commentary, business.industry, Angiotensin II, Respiration, blood-brain barrier, medicine.disease, angiotensin drive to breathe, 030104 developmental biology, medicine.anatomical_structure, Heart failure, Cardiology, medicine.symptom, business, exercise training, Signal Transduction |
| الوصف: | Diaphragmatic weakness is a feature of heart failure (HF) associated with dyspnea and exertional fatigue. Most studies have focused on advanced stages of HF, leaving the cause unresolved. The long-standing theory is that pulmonary edema imposes a mechanical stress, resulting in diaphragmatic remodeling, but stable HF patients rarely exhibit pulmonary edema. We investigated how diaphragmatic weakness develops in two mouse models of pressure overload-induced HF. As in HF patients, both models had increased eupneic respiratory pressures and ventilatory drive. Despite the absence of pulmonary edema, diaphragmatic strength progressively declined during pressure overload; this decline correlated with a reduction in diaphragm cross-sectional area and preceded evidence of muscle weakness. We uncovered a functional codependence between angiotensin II and β-adrenergic (β-ADR) signaling, which increased ventilatory drive. Chronic overdrive was associated with increased PERK (double-stranded RNA-activated protein kinase R-like ER kinase) expression and phosphorylation of EIF2α (eukaryotic translation initiation factor 2α), which inhibits protein synthesis. Inhibition of β-ADR signaling after application of pressure overload normalized diaphragm strength |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f45708ff2721ee5d54ec52f0dc3e7c57Test https://www.frontiersin.org/article/10.3389/fphys.2018.00554/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f45708ff2721ee5d54ec52f0dc3e7c57 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |