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Angiotensin (Ang) II, the main active member of the renin angiotensin system (RAS), is essential for the maintenance of cardiovascular homeostasis. However, hyperactivation of the RAS causes fibrotic diseases. Ang II has pro-inflammatory actions, and moreover activates interstitial fibroblasts and/or dysregulates extracellular matrix degradation. The discovery of new RAS pathways has revealed the complexity of this system. Among the RAS peptides, alamandine (ALA, Ala1 Ang 1-7) has been identified in humans, rats, and mice, with protective actions in different pathological conditions. ALA has similar effects to its well-known congener, Ang-(1-7), as a vasodilator, anti-inflammatory, and antifibrotic. Its protective role against cardiovascular diseases is well-reviewed in the literature. However, the protective actions of ALA in fibrotic conditions have been little explored. Therefore, in this article, we review the ability of ALA to modulate the inflammatory process and collagen deposition, to serve as an antioxidant, and to mediate protection against functional disorders. In this scenario, we also explore ALA as a promising therapy for pulmonary fibrosis after COVID-19 infection.

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INTRODUCTION: Pulmonary fibrosis (PF) is characterized by an accelerated decline in pulmonary function and has limited treatment options. Alamandine (ALA) is a recently described protective peptide of the renin-angiotensin system (RAS) with essential tasks in several conditions. Our group previously demonstrated that ALA is reduced by 365% in the plasma of patients with idiopathic PF, and thus, it is plausible to believe that stimulation of this peptide could represent an important therapeutic target. In this sense, this study investigates the effects of ALA in an experimental model of PF. MATERIALS AND METHODS: Bleomycin (BLM) was administrated in Wistar rats, and these fibrotic animals were treated with ALA for 14 days. Body weight, histology, respiratory, and hemodynamic parameters were analyzed to study the effects of ALA. RESULTS: ALA treatment attenuated the development of fibrosis (P < 0.0001), reduced respiratory system elastance (P < 0.0001), and preserved weight gain (P < 0.0001) in fibrotic animals without affecting the autonomic control of blood pressure and heart rate. CONCLUSION: The data from this study demonstrate the potential of ALA to alleviate pulmonary fibrosis and improve respiratory system mechanics in vivo. The promising results encourage more detailed investigations of the potential of ALA as a future and efficient antifibrotic.

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The aim of the present study was to analyze the effect of neuromuscular electrical stimulation (NMES) and photobiomodulation (PBMT) on the cardiovascular parameters, hemodynamic function, arterial baroreflex sensitivity (BRS), and autonomic balance (ANS) of rats with heart failure (HF). Male Wistar rats (220-290 g) were organized into five groups: Sham (n = 6), Control-HF (n = 5), NMES-HF (n = 6), PBMT-HF (n = 6), and NMES + PBMT-HF (n = 6). Myocardial infarction (MI) was induced by left coronary artery ligation. Animals were subjected to an eight-week NMES and PBMT protocol. Statistical analysis included the General Linear Model (GLM) followed by a Bonferroni post-hoc test. Rats of the NMES-HF group showed a higher MI area than the Control-HF (P = 0.003), PBMT-HF (P = 0.002), and NMES + PBMT-HF (P = 0.012) groups. NMES-HF and NMES + PBMT-HF showed higher pulmonary congestion (P = 0.004 and P = 0.02) and lower systolic pressure (P = 0.019 and P = 0.002) than the Sham group. NMES + PBMT-HF showed lower mean arterial pressure (P = 0.02) than the Sham group. Control-HF showed a higher heart rate than the NMES-HF and NMES + PBMT-HF (P = 0.017 and P = 0.013) groups. There was no difference in the BRS and ANS variables between groups. In conclusion, eight-week NMES isolated or associated with PBMT protocol reduced basal heart rate, systolic and mean arterial pressure, without influence on baroreflex sensibility and autonomic control, and no effect of PBMT was seen in rats with HF.

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Background The family history of hypertension (FHH) imposes consistent risk for diverse chronic diseases that are accompanied by hypertension. Furthermore, the heart rate variability (HRV) and flow-mediated dilation (FMD) are both related to maximal oxygen uptake (VO2max), and are usually impaired during hypertension Objective To compare the autonomic modulation, the endothelial function (EF) and maximum oxygen uptake (VO2max) of young athletes, separated according to their parents' blood pressure (BP) history, in order to study the influence of their genetic background on those parameters. Methods A total of 46 young male soccer players (18±2 years of age) were divided into four groups: 1-normotensive father and mother (FM-N); 2-only father was hypertensive (F-H); 3-only mother was hypertensive (M-H); 4-father and mother were hypertensive (FM-H). Measurements of BP, FMD, HRV and VO2maxwere performed. The significance level adopted in the statistical analysis was 5%. Results The standard deviation of normal RR intervals (SDNN; FM-N=314±185; FM-H=182.4± 57.8), the square root of the mean squared differences in successive RR intervals (RMSSD; FM-N=248±134; FM-H=87±51), the number of interval differences of successive NN intervals greater than 50ms (NN50; FM-N=367±83.4; FM-H=229±55), the ratio derived by dividing NN50 by the total number of NN intervals (pNN50; FM-N=32.4±6.2; FM-H=21.1±5.3) and the high (HF; FM-N=49±8.9; FM-H=35.3±12) and low-frequency (LF; FM-N=50.9±8.9; FM-H=64.6±12) components, in normalized units (%), were significantly lower in the FM-H group than in the FM-N group (p<0.05). On the other hand, the LF/HF ratio (ms2) was significantly higher (p<0.05). We found no significant difference between the groups in VO2maxand FMD (p<0.05). Conclusions In young male soccer players, the FHH plays a potentially role in autonomic balance impairment, especially when both parents are hypertensive, but present no changes in VO2maxand FMD. In this case, there is a decrease in the sympathetic-vagal control, which seems to precede the endothelial damage (Arq Bras Cardiol. 2020; 115(1):52-58).

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Idiopathic pulmonary fibrosis (IPF) is a severe interstitial disease with a mean survival of about 2.5-5 years after diagnosis. Its pathophysiology is still a major challenge for science. It is known that angiotensin II (Ang-II) binds AT1 receptor (AT1R) and its overactivation induces fibrosis, inflammation and oxidative stress. In contrast, activation of the Mas receptor (Mas-R) by angiotensin 1-7 opposes the harmful effects induced by Ang-II. Thus, our innovative objective was to analyze, in patients' lung with IPF, the balance between AT1R and Mas-R expression and their possible association with pulmonary spirometric parameters: forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%). One cubic centimeter of lung tissue was obtained from IPF patients (n = 6) and from patients without IPF (n = 6) who underwent bronchial carcinoma resection. Receptor expression was quantified using western blot. AT1R expression was significantly higher (34 %) in patients with IPF (P = 0.006), whereas Mas-R was significantly less expressed (54 %) in these patients' lungs (P = 0.046). There was also a positive correlation between Mas-R expression and FEV1% (r = 0.62, P = 0.03) and FVC% (r = 0.58, P = 0.05). Conversely, AT1R expression was negatively correlated with FEV1% (r = 0.80, P = 0.002) and FVC% (r = 0.74, P = 0.006). In conclusion, our results demonstrated an increased expression of AT1R and reduced expression of Mas-R in the lung of patients with IPF. The dominance of AT1R expression is associated with reduced lung function, highlighting the role of the renin-angiotensin system peptides in the pathophysiology of IPF.

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Resumo Fundamento A história familiar de hipertensão (HFH) é um fator de risco consistente para diversas doenças crônicas que são acompanhadas por hipertensão. Além disso, a variabilidade da frequência cardíaca (VFC) e a vasodilatação mediada pelo fluxo (VMF), ambas relacionadas ao consumo máximo de oxigênio (VO2max), são geralmente prejudicadas durante a hipertensão. Objetivo Comparar a modulação autonômica, a função endotelial (FE) e o consumo máximo de oxigênio (VO2max) de jovens atletas, separados de acordo com a história de pressão arterial (PA) dos seus pais, a fim de investigar a influência da ascendência genética nesses parâmetros. Métodos Quarenta e seis jovens jogadores de futebol do sexo masculino (18±2 anos) foram divididos em quatro grupos: 1- pai e mãe normotensos (FM-N); 2- apenas pai hipertenso (F-H); 3- apenas mãe hipertensa (M-H); 4- pai e mãe hipertensos (FM-H). Foram realizadas medições da PA, VMF, VFC e do VO2max. Na análise estatística, foi adotado o nível de significância de 5%. Resultados O desvio padrão dos intervalos RR normais (SDNN; FM-N=314±185; FM-H=182,4± 57,8), a raiz quadrada das médias quadráticas das diferenças dos intervalos R-R sucessivos (RMSSD; FM-N=248±134; FM-H=87±51), o número de diferenças entre intervalos NN sucessivos maiores que 50 ms (NN50; FM-N=367±83,4; FM-H=229±55), a proporção de NN50 dividida pelo número total de NNs (pNN50; FM-N=32,4±6,2; FM-H=21,1±5,3) e os componentes de alta (HF; FM-N=49±8,9; FM-H=35,3±12) e baixa frequência (LF; FM-N=50,9±8,9; FM-H=64,6±12), em unidades normalizadas (%), foram significativamente mais baixos no grupo FM-H do que no grupo FM-N (p<0,05). Por outro lado, a relação LF/HF (ms2) foi significativamente maior (p<0,05). Não foram encontradas diferenças significativas no VO2max e na VMF entre os grupos (p<0,05). Conclusão Em jovens jogadores de futebol do sexo masculino, a HFH desempenha um papel potencialmente importante no comprometimento do balanço autonômico, principalmente quando ambos os pais são hipertensos, mas não apresentam alterações no VO2max e na VMF. Nesse caso, há uma diminuição no controle simpatovagal, que parece preceder o dano endotelial. (Arq Bras Cardiol. 2020; 115(1):52-58)

Abstract Background The family history of hypertension (FHH) imposes consistent risk for diverse chronic diseases that are accompanied by hypertension. Furthermore, the heart rate variability (HRV) and flow-mediated dilation (FMD) are both related to maximal oxygen uptake (VO2max), and are usually impaired during hypertension Objective To compare the autonomic modulation, the endothelial function (EF) and maximum oxygen uptake (VO2max) of young athletes, separated according to their parents' blood pressure (BP) history, in order to study the influence of their genetic background on those parameters. Methods A total of 46 young male soccer players (18±2 years of age) were divided into four groups: 1-normotensive father and mother (FM-N); 2-only father was hypertensive (F-H); 3-only mother was hypertensive (M-H); 4-father and mother were hypertensive (FM-H). Measurements of BP, FMD, HRV and VO2maxwere performed. The significance level adopted in the statistical analysis was 5%. Results The standard deviation of normal RR intervals (SDNN; FM-N=314±185; FM-H=182.4± 57.8), the square root of the mean squared differences in successive RR intervals (RMSSD; FM-N=248±134; FM-H=87±51), the number of interval differences of successive NN intervals greater than 50ms (NN50; FM-N=367±83.4; FM-H=229±55), the ratio derived by dividing NN50 by the total number of NN intervals (pNN50; FM-N=32.4±6.2; FM-H=21.1±5.3) and the high (HF; FM-N=49±8.9; FM-H=35.3±12) and low-frequency (LF; FM-N=50.9±8.9; FM-H=64.6±12) components, in normalized units (%), were significantly lower in the FM-H group than in the FM-N group (p<0.05). On the other hand, the LF/HF ratio (ms2) was significantly higher (p<0.05). We found no significant difference between the groups in VO2maxand FMD (p<0.05). Conclusions In young male soccer players, the FHH plays a potentially role in autonomic balance impairment, especially when both parents are hypertensive, but present no changes in VO2maxand FMD. In this case, there is a decrease in the sympathetic-vagal control, which seems to precede the endothelial damage (Arq Bras Cardiol. 2020; 115(1):52-58)

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Patients were separated into two groups: (1) non-waiting list (NWL) and (2) waiting list (WL) for the lung transplantation. We found greater levels of the faith and spirituality, in those awaiting transplantation. In the NWL group, higher 'meaning' was associated with higher 'vitality,' 'emotional well-being,' and 'mental health'; higher 'peace' was associated with higher 'mental health.' In the WL group, higher 'peace' was associated with and better 'mental health' and 'emotional well-being.' Regardless of whether patients are lung transplantation candidates or not, spirituality/religiosity may help those with lung diseases cope better with their disease and have better quality of life.

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