FUNCTIONAL EVALUATION, AND MOLECULAR STRUCTURE OF NEUROMUSCULAR JUNCTION IN DIAPHRAGM MUSCLE OF RATS WITH HEART FAILURE UNDERGOING TRAINING TO AEROBIC

Abstract

Heart failure (HF) is a syndrome characterized by reduced cardiac function and activation of compensatory mechanisms in the body. The most common symptoms are fatigue and dyspnea, as well as changes in muscle fiber types from slow to fast, atrophy and increased expression of the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction (NMJ). The stability of nAChR activation and occurs by the interaction of proteins with trophic factors sarcolemma of the muscle fiber. The diaphragm is affected by the IC and physical training is considered a widely accepted practice to minimize the consequences of symptoms caused by IC. Our working hypothesis is that in HF, the increased expression of nAChRs is associated with changes in the release of trophic factors that act in the expression of proteins of the sarcolemma, leading to changes in the phenotype of the diaphragm. In addition, exercise minimizes changes in the endplates and the morphological and functional characteristics of the muscle. This study will evaluate the gene and protein expression of ± and µ subunits of nAChRs, the trophic factor agrina and proteins of the sarcolemma rapsina and musk; evaluate changes in neuromuscular activity through functional analysis, as well as the characterization and structural analysis of fiber-specific endplates in the diaphragm of rats with HF, submitted to aerobic training. Will be used 112 male Wistar rats (90 to 100g) were divided into four groups: Control (C), aortic stenosis (AoS - insertion of a silver clip of 0.6 mm in diameter in the ascending aorta), Trained (TR), Aortic Stenosis Training with (EAoTR). After 18 weeks of surgical induction of AOS, part of the control animals and with AOS will be randomly divided into trained or not. The animals will be submitted to aerobic training on a treadmill for 10 weeks (5days/week). The clinical parameters of the IC will be evaluated. The gene and protein expression of ± and µ subunits of nAChRs, the trophic factor Agrina and proteins of the sarcolemma of the muscle fiber and musk rapsina will be analyzed by RT-PCR and Western blot, respectively. The neuromuscular activity will be assessed by analyzing the functional and structural characterization of fiber-specific endplates will be performed by confocal laser scanning. The data will be submitted to appropriate statistical analysis.