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Role of kinins in the anti-inflammatory effects of aerobic training in experimental models of Asthma

Grant number: 19/05739-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2019
Effective date (End): October 31, 2022
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Rodolfo de Paula Vieira
Grantee:Maysa Alves Rodrigues Brandão Rangel
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Asthma is a chronic inflammatory disease of the airways, resulting in worsening of quality of life. This worsening presents a correlation with airflow limitation and with bronchial hyperresponsiveness. The cellular and molecular mechanism involved in the bronchial hyperresponsiveness is limited. However, it was already demonstrated an important role of kinins in the bronchial hyperresponsiveness of asthmatic patients as well as in experimental models. Beyond that, the kinins also present other effects on asthmatic phenotype, which include: bronchoconstriction, increased vascular permeability, increased mucus secretion by bronchial epithelium, increased cholinergic and sensorial stimulation. In this way, antagonists of kinins receptors, peptides and non-peptides, have demonstrated potential beneficial effects for inhibition of asthmatic phenotype. On the other side, several studies have demonstrated that aerobic physical training (APT), performed in proper manner present inhibitory effects on asthmatic phenotype, including reduction of chronic allergic pulmonary inflammation, hyperresponsiveness, mucus hypersecretion and exacerbation of Th2 immune response. However, until this moment, only few cellular and molecular mechanisms involved in these effects of APT were studied. Thus, the present project aims to evaluate if the beneficial effects of APT (reduction of pulmonary inflammation, mucus production, bronchial remodeling, improvement of pulmonary mechanics and of bronchial hyperresponsiveness) in an experimental model of Asthma (using House Dust Mite - HDM - Dermatophagoides pteronyssinus) is mediated via kinins and its respective receptors, peptides and non-peptides. To do that, 80 male C57Bl/6 mice, 6-8 weeks of age, will be divided in 4 experimental groups (n = 20), Control (Co), Exercise (Ex), Asthma (As) and Asthma + Exercise (As + Ex). The animals will receive HDM (100ug/mouse), 3x/week, during 6 weeks. The APT will be performed in ergometric treadmill, at moderate intensity, 5x/week, 1h/session, during 4 weeks, beginning in the third week of the experimental protocol. Then, the therapeutic effects of APT in an experimental model of Asthma will be evaluated, since the training will begin after the establishment of asthmatic phenotype (after the second week of HDM administration). (AU)