Effects of captopril on cardiovascular reflexes and respiratory mechanisms in rats submitted to monocrotaline-induced pulmonary arterial hypertension.

BACKGROUND: Pulmonary Arterial Hypertension (PAH) is a disease associated with increased arteriolar resistance in the lungs. Due to hypoxemia, some physiological mechanisms can be posteriorly affected, including respiratory and cardiovascular reflexes, but this has not yet been fully investigated. This study aimed to evaluate how these mechanisms were affected by monocrotaline (MCT)-induced PAH and the possible therapeutic role of angiotensin converting enzyme inhibitor (ACEi), captopril, in reversing this remodeling process. METHODS AND RESULTS: Groups of Wistar rats received MCT injections (60 mg kg(-1)). Three weeks later, they received captopril (CPT, 100 mg kg(-1)) in their drinking water (MCT + CPT) or water alone (MCT) for 2 weeks. As control, saline-treated animals received captopril in their drinking water (CPT) or water alone (CON), also for 2 weeks. Results showed that PAH was fully induced in the MCT group, evidenced by a high pulmonary index. Gasometrical and respiratory analyses showed hypoxemia and compensatory hyperventilation. CPT treatment brought these parameters to similar values to those observed in the CON group. We observed that autonomic dysfunction in the MCT group was suppressed by CPT. Finally, cardiovascular reflexes analysis showed increased chemoreflex responses in the MCT group, while baroreflex sensibility was decreased. Surprisingly, CPT normalized these reflex responses to values similar to the CON group. CONCLUSIONS: The present study demonstrates that MCT-induced PAH induces compensatory respiratory responses, dysautonomia, and baroreflex dysfunction and increases chemoreflex responses. The data also indicate that CPT was effective in reversing these cardio-respiratory disorders, suggesting that ACEi could be a potential therapeutic target for PAH.

Strengthening exercises improve symptoms and quality of life but do not change autonomic modulation in fibromyalgia: a randomized clinical trial.

OBJECTIVE: Autonomic dysfunction is an important mechanism that could explain many symptoms observed in fibromyalgia (FM). Exercise is an effective treatment, with benefits potentially mediated through changes in autonomic modulation. Strengthening is one of the less studied exercises in FM, and the acute and chronic effects of strengthening on the autonomic system remain unknown. The objective of this study was to assess the chronic effects of strengthening exercises (STRE) on autonomic modulation, pain perception and the quality of life (QOL) of FM patients. METHODS: Eighty sedentary women with FM (ACR 1990) were randomly selected to participate in STRE or flexibility (FLEX) exercises in a blinded controlled trial. The intensity of STRE was set at 45% of the estimated load of 1 Repetition Maximum (RM) in 12 different exercises. Outcomes were Visual Analog Scale (VAS) for pain, Heart Rate Variability (HRV) analysis, treadmill test, the sit and reach test (Wells and Dillon's Bench), maximal repetitions test and handgrip dynamometry; and quality of life by the Fibromyalgia Impact Questionnaire (FIQ), the Beck and Idate Trait-State Inventory (IDATE), a short-form health survey (SF-36). RESULTS: The STRE group was more effective to strength gain for all muscles and pain control after 4 and 16 weeks (p<0.05). The FLEX group showed higher improvements in anxiety (p<0.05). Both groups showed improvements in the QOL, and there was no significant difference observed between the groups. There was no change in the HRV of the STRE and FLEX groups. CONCLUSIONS: Strengthening exercises show greater and more rapid improvements in pain and strength than flexibility exercises. Despite the benefits in fitness, pain, depression, anxiety and quality of life, no effect was observed on the autonomic modulation in both groups. This observation suggests that changes in autonomic modulation are not a target tobe clinically achieved in fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02004405.

Uso crônico de decanoato de nandrolona como fator de risco para hipertensão arterial pulmonar em ratos Wistar / Chronic use of nandrolone decanoate as risk factor for pulmonary arterial hypertension in Wistar rats

INTRODUÇÃO: O uso indiscriminado de esteróides anabolizantes sintéticos, análogos à testosterona, implica aumento do risco cardiovascular e hipertrofia cardíaca. Assim, o aumento da massa ventricular direita corrigido pelo peso corporal (i.é., hipertrofia ventricular direita - HVD), poderia elevar o risco para o desenvolvimento de hipertensão arterial pulmonar (HAP). OBJETIVOS: Examinar os efeitos do tratamento em longo prazo com decanoato de nadrolona na HVD e sua relação com a HAP em ratos. MÉTODOS: 16 ratos Wistar com três meses de idade foram aleatoriamente divididos em dois grupos: 1) controle-sham (CONT, n = 8); 2) tratados com decanoato de nandrolona (DECA, n = 8). O tratamento consistiu na aplicação intramuscular de Deca-durabolin® 6.0mg.kg-1 de peso corporal durante quatro semanas. Após tratamento, os animais foram anestesiados com hidrato de cloral (4.0mL.kg-1, i.p.), submetidos à cateterização da artéria femoral para registro da pressão arterial media (PAM) e frequência cardíaca (FC). O coração, os rins e o fígado foram retirados, pesados e avaliados os índices de hipertrofia, os quais foram calculados pela razão da massa do órgão pelo peso corporal (mg.g-1). RESULTADOS: Os animais tratados com DECA apresentaram aumento (p < 0,01) do peso corporal (338 ± 6g) vs. CONT (315 ± 5g). Não houve alterações da PAM, embora houvesse (p < 0,01) bradicardia nos animais tratados com DECA (321 ± 13bpm) vs. CONT (368 ± 11bpm). Verificou-se significativa (p < 0,01) hipertrofia dos ventrículos e rins, mas não no fígado. A correlação entre a HVD e PAM no grupo DECA apresentou coeficiente de Pearson positivo e maior (r² = 0,4013) quando comparado com o controle (r² = 0,0003). CONCLUSÕES: Esses dados demonstram que o uso em longo prazo de decanoato de nandrolona induz importante bradicardia e HVD, o que sugere aumento do risco para HAP.

INTRODUCTION: The unsystematic use of anabolic steroids, synthetic analogs of testosterone, implies enhanced cardiovascular risk and cardiac hypertrophy. Thus, increased right ventricular mass corrected by the body weight (e.g.right ventricular hypertrophy -RVH) could raise the risk for development of pulmonary arterial hypertension (PAH). OBJECTIVES: to examine the effects of long-term chronic treatment with nandrolone decanoate on the RVH and its relationship with PAH in rats. METHODS: 16 three-month Wistar male rats were treated with nandrolone decanoate (6.0 mg/kg-1 body weight; DECA, n=8) or control vehicle (CONT, n=8). The drug and vehicle were administered by a single injection in the femoral muscle once a week for 4 weeks. After the treatment, rats were anesthetized with chloral hydrate (4.0mL/kg-1, ip), and catheterized in the femoral artery. Twenty-four hours later, mean arterial pressure (MAP) and heart ratio were measured. The heart, kidneys and liver were removed, weighed and the rates of hypertrophy (RH) were measured, which were calculated by the ratio of the weight of the organs by the body weight (mg.g-1). RESULTS: DECA treatment increased body weight (338 ± 6g; p <0.01) vs. CONT (315 ± 5g). This treatment had no effect on the MAP (CONT, 110±4mmHg, DECA, 113 ± 4mmHg). However, the bradycardia of animals treated with DECA (321 ± 13bpm, p<0.01) was significantly lower than that of CONT (368 ±11bpm). RH increased (p <0.01) the cardiac ventricles and the kidneys, but not in the liver. The correlation between the RVH and MAP in DECA showed positive and higher Pearson's coefficient (r² = 0.4013) vs CONT (r² = 0.0003). CONCLUSIONS: It was concluded that chronic nandrolone decanoate treatment induced bradycardia and RVH, which suggests increased risk for PAH.