Effect of the aerobic physical training in the chronic obstructive pulmonary disease: relevance to lung inflammation, oxidative stress and cardiovascular autonomic modulation

A exacerbação da doença pulmonar obstrutiva crônica (DPOC) é uma manifestação sistêmica na qual o processo inflamatório pulmonar, principalmente em resposta à vírus ou bactérias, é o principal fator de agravamento da DPOC. É caracterizada pela intensa neutrofilia associada à secreção de mediadores pró-inflamatórios e proteases, pelo desequilíbrio dos mecanismos pró e antioxidantes, e pela piora da função pulmonar, associado à alterações sistêmicas, como distúrbios autonômicos relacionados à um mau prognóstico. Atualmente não há tratamento farmacológico seletivo para a exacerbação da DPOC, além de promover efeitos colaterais graves. Além disso, há poucos estudos que avaliam a exacerbação da DPOC em um curto período de exposição à fumaça e ao LPS de Escherichia coli. Sendo assim, a investigação do mecanismo de ação de terapias não-farmacológicas para o controle da exacerbação da DPOC em modelos de curta exposição se fazem relevantes. Assim, o presente estudo investigou o efeito protetor do TFA moderado em esteira ergométrica na exacerbação da DPOC induzida pela fumaça de cigarro associada ao desafio com LPS em camundongos C57Bl/6. Decorrido 4 semanas do TFA, a DPOC foi induzida (D28-30) e, 24 h depois, foi realizada a eutanásia (D31). Nossos resultados mostram que um curto período de exposição ao cigarro associado ao agente infeccioso LPS foi capaz de induzir exacerbação da resposta inflamatória no modelo in vivo de DPOC adotado no presente estudo. O TFA atenuou a inflamação neutrofílica no lavado broncoalveolar (LBA), a expressão de TLR no pulmão, a secreção de mediadores pró-inflamatórios, pró-oxidantes e proteases no LBA, a peroxidação lipídica e a expressão de NF-κB, STAT3 e SOCS3 pulmonar, e a atividade simpática cardíaca. Por fim, nossos resultados mostram que TFA apresenta efeito antiinflamatório, antioxidante, e restaura a modulação autonômica cardiovascular em um modelo de exacerbação da DPOC.The exacerbation of chronic obstructive pulmonary disease (COPD) is a systemic manifestation in which a pulmonary inflammatory process, mainly in response to viruses or bacteria, is the main factor that worsens COPD. The exacerbation of pulmonary inflammation in COPD is characterized by intense neutrophil infiltration followed by secretion of pro-inflammatory mediators and proteases, by the imbalance of pro and antioxidant mechanisms and by the worsening of lung function, associated with systemic alterations, such as autonomic disorders, which are related with a poor prognosis. Currently, there is no selective pharmacological treatment for exacerbation of COPD. In addition, there are few studies that assess the exacerbation of COPD in a short period of exposure to smoke and Escherichia coli LPS. For this reason, it is relevant to investigate the mechanism of action of non-pharmacological therapies to control the exacerbation of COPD that have few side effects. In this sense, aerobic physical training (APT) meets these requirements. Considering this, the present study investigated the protective effect of moderate TFA performed in a treadmill on exacerbation of COPD induced by cigarette smoke in association with the challenge with LPS in C57Bl/6 mice. After 1 month of moderate APT, COPD was induced and, 24h after, euthanasia was performed. Our results show that a short period of exposure to cigarettes associated with the infectious agent LPS induced exacerbation of the inflammatory response in the in vivo model of COPD adopted in the present study. APT attenuated neutrophilic inflammation in bronchoalveolar lavage (BAL), the expression of TLR in the lung, the secretion of pro-inflammatory, pro-oxidants and proteases in BAL, lipid peroxidation and the expression of pulmonary NF-κB, STAT3 and SOCS3 and cardiac sympathetic activity. Finally, our results show that TFA had an anti-inflammatory and antioxidant effect and it restored cardiac autonomic balance in a model of exacerbation of COPD.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Exercise training ameliorates adrenergic control in spontaneously hypertensive rats

The goal of this study was to examine vascular control after sympathetic stimulation by tyramine infusion in hypertensive rats submitted to swimming training. To this end, male rats were assigned to the following groups: sedentary (SN) and trained normotensive (TN), sedentary (SH) and trained hypertensive (TH). Arterial pressure (AP), heart rate (HR), HR variability (HRV), AP variability (APV), and cardiac autonomic function were recorded. Following, infusion of tyramine was administrated. The TN and TH showed a lower resting HR compared with their respective sedentary groups (p < .05). Pressure levels were less in TH than SH (p < .05). The TH showed a higher HRV together with a lower APV in comparison to SH (p < .05). The sympathetic modulation of HRV and APV was lower in TH than in SH (p < .05). Both trained groups presented an increased parasympathetic modulation of HRV compared with their respective sedentary groups (p < .05). The TN and TH groups had a higher vagal effect in comparison with their respective sedentary groups (p < .001). The sympathetic effect was lower in TH than in SH (p < .001). Pressor and HR responses to tyramine in different doses were attenuated in TH (p < .001). Further analysis showed a significant association between infusion of tyramine and normalized LF component of HRV (r = 0.84, p < .001), systolic APV (r = 0.58, p < .001) and diastolic APV (r = 0.49, p < .001). In conclusion, exercise training provokes less pressor response variation by tyramine infusion in hypertensive animals suggesting sympathetic nerve endings adjustments and decrease of the vasoconstrictor effect attenuates injury caused by hypertension improving cardiovascular autonomic dysfunction, which can be associated with sympathetic attenuation