Oral administration of angiotensin-(1-7) decreases muscle damage and prevents the fibrosis in rats after eccentric exercise

Abstract

New findings: What is the central question of this study? Eccentric contraction exercises cause damage to muscle fibres and induce inflammatory responses. The exacerbation of this process can induce deposition of fibrous connective tissue, leading to decreased muscle function. The aim of this study was to examine the role of angiotensin-(1-7) in this context. What is the main finding and its importance? Our results show that oral treatment with angiotensin-(1-7) decreases muscle damage induced by eccentric exercise, reducing inflammation and fibrosis in the gastrocnemius and soleus muscles. This study shows a potential effect of angiotensin-(1-7) for the prevention of muscle injuries induced by physical exercise.

Abstract: Eccentric contraction exercises cause damage to the muscle fibres and induce an inflammatory reaction. The protective effect of angiotensin-(1-7) [Ang-(1-7)] in skeletal muscle has led us to examine the role of this peptide in modifying processes associated with inflammation and fibrogenesis induced by eccentric exercise. In this study, we sought to investigate the effects of oral administration of Ang-(1-7) formulated in hydroxypropyl β-cyclodextrin (HPβ-CD) in prevention and treatment of muscle damage after downhill running. Male Wistar rats were divided into three groups: control (untreated and not exercised; n = 10); treated/exercised HPβ-CD Ang-(1-7) (n = 40); and treated/exercised HPβ-CD (n = 40). Exercised groups were subjected to a single eccentric contraction exercise session on a treadmill inclined to -13° at a constant speed of 20 m/min, for 60 min. Oral administration of HPβ-CD Ang-(1-7) and HPβ-CD was performed 3 h before the exercise protocol and daily as a single dose, until the end of the experiment. Samples were collected 4, 12, 24, 48 and 72 h after the exercise session. The animals treated with the Ang-(1-7) showed lower levels of creatine kinase, lower levels of tumor necrosis factor-α in soleus muscle and increased levels of interleukin-10 cytokines. The inflammatory cells and deposition of fibrous connective tissue in soleus and gastrocnemius muscles were lower in the group treated with Ang-(1-7). The results of this study show that treatment with an oral formulation of Ang-(1-7) enhances the process of repair of muscle injury induced by eccentric exercise.

Keywords: angiotensin-(1-7); eccentric exercise; fibrosis; inflammation; muscle damage.