Role of Irisin, induced by combined physical training or exogenous, in the attenuation of arterial hypertension, arterial stiffness and muscle atrophy in rats treated with dexamethasone.

• Grant number: 24/03275-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Sandra Lia do Amaral Cardoso
• Grantee: Sandra Lia do Amaral Cardoso
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil
• Associated researchers: Carlos Ferreira dos Santos ; Thiago José Dionísio

Abstract

We previously demonstrated that physical preconditioning mitigates several side effects caused by chronic treatment with dexamethasone (DEX), including hypertension, arterial stiffening, and muscle atrophy. The mechanisms responsible for these responses are not yet fully elucidated. Recently, Irisin, a novel myokine induced by physical exercise, has gained visibility and has been considered a possible mediator of responses to physical training. However, despite evidence of beneficial effects of physical training in rats treated with DEX, nothing is known about the contribution of Irisin in this context, much less about the possible beneficial effects of treatment with Irisin in individuals treated with DEX. Thus, the objective of the present study will be to evaluate the role of Irisin in the benefits of combined physical training on hemodynamic and muscular parameters in rats treated with DEX, as well as to evaluate the effects of treatment with exogenous Irisin in sedentary rats treated with DEX. To answer these questions, this project will combine functional (blood pressure and assessment of arterial stiffness), structural (area of skeletal muscle fibers) and molecular (production of inflammatory markers and constituents of the extracellular matrix in vessels) techniques in sedentary or trained animals and treated or not with DEX. These measurements will also be associated with molecular assessments of the amount of Irisin and its precursors in the vessel and blood, which appear to be involved in the beneficial responses to physical training. It is hypothesized that the attenuation of hypertension, arterial stiffness and muscular atrophy induced by combined physical training involves the participation of Irisin and, if this is true, chronic treatment with exogenous Irisin will be able to attenuate the increase these side effects known to be caused by DEX treatment in normotensive animals. Understanding the mechanisms induced by physical exercise, involving Irisin, or its exogenous effects, may open new therapeutic perspectives and preventive strategies for cardiovascular and musculoskeletal diseases induced by DEX treatment. (AU)