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1.
Respir Physiol Neurobiol ; 274: 103358, 2020 03.
Article in English | MEDLINE | ID: mdl-31811939

ABSTRACT

Mammals airways are extensively innervated by the vagus nerve, which controls the airway diameter and bronchial tone. However, very few studies described the respiratory function and lung morphology after vagal section. In the present study, we evaluated the respiratory mechanics after aerosolization of vehicle (to obtain control values), a muscarinic agonist (methacholine), a ß2-adrenergic agonist (salbutamol) or a muscarinic antagonist (ipratropium bromide) in intact (Vi) and bilaterally vagotomized (Vx) Swiss male mice. Different group was established for morphometric analyze. The total lung resistance, airway resistance, elastance, compliance, lung tissue damping, lung tissue elastance, and morphological parameters (collagen and elastic fibers) were significantly different in the Vx group compared to the Vi group. Bronchoconstrictor and bronchodilators change the respiratory function of the Vx group. In conclusion, the vagus nerve modulates the lung function in response to bronchoconstriction and bronchodilation, as well as lung architecture of mice.


Subject(s)
Adrenergic beta-2 Receptor Agonists/pharmacology , Bronchoconstrictor Agents/pharmacology , Bronchodilator Agents/pharmacology , Lung/drug effects , Lung/physiology , Muscarinic Antagonists/pharmacology , Respiratory Mechanics/drug effects , Respiratory Mechanics/physiology , Vagotomy , Vagus Nerve/physiology , Albuterol/pharmacology , Animals , Collagen , Elastic Tissue , Ipratropium/pharmacology , Lung/ultrastructure , Male , Methacholine Chloride/pharmacology , Mice , Muscarinic Agonists/pharmacology
2.
Mol Cell Endocrinol ; 474: 151-157, 2018 10 15.
Article in English | MEDLINE | ID: mdl-29522858

ABSTRACT

Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite elevated levels of cortisol. Within this context, knowledge of the transcriptional pattern of the GR gene in response to variations in physiological parameters may shed light on this issue. We addressed this problem by measuring plasmatic corticosterone (CCT) levels and assessing GR expression at transcript and protein levels in rats with caecal ligation and puncture (CLP)-induced ARDS-like syndrome treated with dexamethasone and metyrapone. Seventy male rats were randomized into three main groups: Naïve (any treatment), Sham (caecum-exposed) and CLP. CLP animals were divided into three groups according to pretreatments performed before surgery: CLP sal (0.9% NaCl ip), CLP metyrapone (50 mg.kg-1 ip) and CLP dexamethasone (0.5 mg.kg-1 ip). Our results showed that CLP sal promotes elevation in CCT levels, which are significantly reduced with metyrapone to levels comparable to untreated animals when dexamethasone is used. In this hormonal milieu, the GR gene transcript levels of both variants, GRα and GRß, are produced in comparable levels and in response to caecum-exposing surgery. Nonetheless, the expression of the GRα variant demonstrated positive sensitivity to variations in CCT levels and was downregulated in animals treated with dexamethasone. Moreover, nuclear translocation of GR protein decreased with high levels of plasma CCT and higher GR translocation was found in animals with moderate CCT levels; in either case, the process seemed to be positively associated with the CLP procedure.


Subject(s)
Cecum/pathology , Dexamethasone/therapeutic use , Gene Expression Regulation/drug effects , Metyrapone/therapeutic use , Receptors, Glucocorticoid/genetics , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/genetics , Animals , Corticosterone/blood , Dexamethasone/pharmacology , Disease Models, Animal , Ligation , Male , Metyrapone/pharmacology , Punctures , Rats, Wistar , Receptors, Glucocorticoid/metabolism , Respiratory Distress Syndrome/pathology , Transcription, Genetic
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