Kátia De Angelis

The beneficial effects of exercise in rodents are preserved after detraining: a phenomenon unrelated to GLUT4 expression

BackgroundAlthough exercise training has well-known cardiorespiratory and metabolic benefits, low compliance with exercise training programs is a fact, and the harmful effects of physical detraining regarding these adaptations usually go unnoticed. We investigated the effects of exercise detraining on blood pressure, insulin sensitivity, and GLUT4 expression in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY).MethodsStudied animals were randomized into sedentary, trained (treadmill running/5 days a week, 60 min/day for 10 weeks), 1 week of detraining, and 2 weeks of detraining. Blood pressure (tail-cuff system), insulin sensitivity (kITT), and GLUT4 (Western blot) in heart, gastrocnemius and white fat tissue were measured.ResultsExercise training reduced blood pressure (19%), improved insulin sensitivity (24%), and increased GLUT4 in the heart (+34%); gastrocnemius (+36%) and fat (+22%) in SHR. In WKY no change in either blood pressure or insulin sensitivity were observed, but there was an increase in GLUT4 in the heart (+25%), gastrocnemius (+45%) and fat (+36%) induced by training. Both periods of detraining did not induce any change in neither blood pressure nor insulin sensitivity in SHR and WKY. One-week detraining reduced GLUT4 in SHR (heart: -28%; fat: -23%) and WKY (heart: -19%; fat: -22%); GLUT4 in the gastrocnemius was reduced after a 2-week detraining (SHR: -35%; WKY: -25%). There was a positive correlation between GLUT4 (gastrocnemius) and the maximal velocity in the exercise test (r = 0.60, p = 0.004).ConclusionsThe study findings show that in detraining, despite reversion of the enhanced GLUT4 expression, cardiorespiratory and metabolic beneficial effects of exercise are preserved.

Beneficial effects of treadmill training in experimental diabetic nerve regeneration.

OBJECTIVES: We investigated the effects of treadmill training (10 weeks) on hindlimb motor function and nerve morphometric parameters in diabetic rats submitted to sciatic nerve crush. MATERIALS AND METHOD: Wistar rats (nu200a=u200a64) were divided into the following groups: non-diabetic; trained non-diabetic; non-diabetic with sciatic nerve crush; trained non-diabetic with sciatic nerve crush; diabetic; trained diabetic; diabetic with sciatic nerve crush or trained diabetic with sciatic nerve crush. Diabetes was induced by streptozotocin injection (50 mg/kg, iv). Hindlimb motor function was evaluated weekly by assessing sciatic functional indices, and the proximal and distal portions of the sciatic nerve were used for morphometric analysis. RESULTS: At 13 weeks post-injury, the distal nerve portion of all injured groups and the proximal nerve portion of the diabetic with sciatic nerve crush group presented altered morphometric parameters such as decreased myelinated fiber diameter (∼7.4±0.3µm vs ∼4.8±0.2µm), axonal diameter (∼5±0.2µm vs ∼3.5±0.1µm) and myelin sheath thickness (∼1.2±0.07µm vs ∼0.65±0.07µm) and an increase in the percentage of area occupied by endoneurium (∼28±3% vs ∼60±3%). In addition, in the non-diabetic with sciatic nerve crush group the proximal nerve portion showed a decreased myelinated fiber diameter (7.4±0.3µm vs 5.8±0.3µm) and myelin sheath thickness (1.29±0.08µm vs 0.92±0.08µm). The non-diabetic with sciatic nerve crush, trained non-diabetic with sciatic nerve crush, diabetic with sciatic nerve crush and trained diabetic with sciatic nerve crush groups showed normal sciatic functional index from the 4th, 4th, 9th and 7th week post-injury, respectively. Morphometric alterations in the proximal nerve portion of the diabetic with sciatic nerve crush and non-diabetic with sciatic nerve crush groups were either prevented or reverted to values similar to the non-diabetic group by treadmill training. CONCLUSION: Diabetic condition promoted delay in sciatic nerve regeneration. Treadmill training is able to accelerate hindlimb motor function recovery in diabetic injured rats and prevent or revert morphometric alterations in proximal nerve portions in non-diabetic and diabetic injured rats.

Hypercholesterolemia magnitude increases sympathetic modulation and coagulation in LDLr knockout mice

We investigated the effects of low lipoprotein receptor deficiency in cholesterol blood concentrations, blood pressure, hemostatic factors, and the autonomic nervous system in three groups: control mice fed standard diet (CO, n=9), lipoprotein receptor-deficient mice (LDLr(-/-), n=9) fed standard diet (LDLr-S) or hypercholesterolemic diet (LDLr-H, n=8). Frequency domain analysis of heart rate and blood pressure variability was performed with an autoregressive algorithm. The spectral components were expressed in absolute (s(2) or mmHg(2)) and normalized units. Spontaneous baroreflex sensitivity (BRS) was estimated by alpha index, defined as square root ratio between low frequency power in blood pressure variability and heart rate variability. LDLr/- mice presented a significant increase in the cholesterol blood concentration (mean±SD; mg/dl; LDLr-S=202.01±34.38 and LDLr-H=530.7±75.17) compared to CO (79.2±13.6), p=0.001. The receptor deletion was associated with a heart rate variability reduction (p=0.013). The BRS was reduced (p<0.05) in LDLr-S and LDL-H (mean±SD: 0.96±0.39 and 0.59±0.34, respectively) compared to CO (4.02±1.92). Moreover, hypercholesterolemic diet significantly increased the cardiac sympathetic modulation (0V pattern of symbolic analysis: mean±SD, CO=8.04±4.53; LDLr-S=16.49±4.52 and LDLr-H=21.80±8.24, p=0.006). The 0V pattern was statically correlated to coagulation factor VII (r=0.555, p=0.0208). In LDLr-H, the concentration (interquartile range) of plasmatic fibrinogen and hemostatic factors VII (2.8-3.3) and XII (1.1-1.3) were increased compared to CO (0.9-1.1and 0.9-1.0, respectively) and LDLr-S (0.7-1.0 and 0.8-0.9, respectively) (p<0.004 for FVII and p<0.006 for FXII). Taken together, the results indicate that plasmatic cholesterol magnitude is determinant to increase the coagulation and the sympathetic modulation.

Change in central kinin B2 receptor density after exercise training in rats

Cardiovascular responses elicited by the stimulation of kinin B2 receptors in the IV cerebral ventricle, paratrigeminal nucleus or in the thoracic spinal cord are similar to those observed during an exercise bout. Considering that the kalikrein-kinin system (KKS) could act on the cardiovascular modulation during behavioral responses as physical exercise or stress, this study evaluated the central B2 receptor densities of Wistar (W) and spontaneously hypertensive rats (SHR) after chronic moderate exercise. Animals were exercise-trained for ten weeks on a treadmill. Afterwards, systolic blood pressure decreased in both trained strains. Animals were killed and the medulla and spinal cord extracted for B2 receptor autoradiography. Trained animals were compared to their sedentary controls. Sedentary groups showed specific binding sites for Hoe-140 (fmol/mg of tissue) in laminas 1 and 2 of the spinal cord, nucleus of the solitary tract (NTS), area postrema (AP), spinal trigeminal tract (sp5) and paratrigeminal nucleus (Pa5). In trained W a significant increase (p<0.05) in specific binding was observed in the Pa5 (31.3%) and NTS (28.2%). Trained SHR showed a significant decrease in receptor density in lamina 2 (21.9%) of the thoracic spinal cord and an increase in specific binding in Pa5 (36.1%). We suggest that in the medulla, chronic exercise could hyper stimulate the KKS enhancing their efficiency through the increase of B2 receptor density, involving this receptor in central cardiovascular control during exercise or stress. In the lamina 2, B2 receptor might be involved in the exercise-induced hypotension.

Disfunção autonômica cardiovascular no diabetes mellitus experimental

Much new information has been published in the last few years regarding pathophysiology of cardiovascular autonomic dysfunction in diabetic rats and mice. Our group has been studying the time-course cardiovascular changes associated with experimental diabetes in the last years, and obtained consistent evidences of severe dysautonomia in diabetes animal models. The aim of this manuscript is to review the contribution that studies involving different animal models of insulin deficiency or resistance have given to understand, treat and prevent diabetic cardiovascular autonomic dysfunction.

Efeitos cardiovasculares da abstinência do fumo no repouso e durante o exercício submáximo em mulheres jovens fumantes

OBJECTIVE: The objective of the present study was to verify the effect of tobacco smoking abstinence on cardiovascular responses to progressive submaximal physical exercise in sedentary female smokers. METHODS: Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were non-invasively measured in young non-smoking women (NSW, n = 7) and smoking women (SW, n = 7), with and without tobacco abstinence for 24 hours, at rest, during the accomplishment of a submaximal bicycle ergometric test and recovery period. RESULTS: At rest, DBP and HR were higher in the SW group (76 ± 1 mmHg and 86 ± 5 bpm) when compared to the NSW group (68 ± 2 mmHg and 72 ± 2 bpm). After 24 hours of no tobacco use, the groups presented similar values. During exercise, SBP and HR increased in the studied groups. DBP was higher in the SW group (~15%) in relation to the NSW group in all periods of exercise training. In the abstinence period, DBP only increased in the last load of exercise. During recovery period, in basal condition and 24h-abstinence, both DBP and HR were higher in the SW group when compared to the NSW group. CONCLUSION: These results show that young female smokers present harmful consequences in hemodynamic parameters at rest and in response to submaximal exercise. These findings can be partly reverted by short-term abstinence from tobacco use.

História familiar positiva de diabetes altera a resposta cronotrópica ao exercício agudo

The aim of this study was to verify the effects of one aerobic exercise session (AES) on the metabolic and hemodynamic profile in diabetes type II offspring. Healthy young males were assigned into 2 groups: diabetic offspring (DO, n=7) and euglicemic offspring (EO, n=7). Metabolic (triglycerides and glucose levels) and cardiovascular (arterial pressure, AP, heart rate, HR) measures were realized before, during and after the AES. The AES was realized on a treadmill during 30 minutes, with progressive intensity. The groups showed similar triglycerides, AP and HR values at rest. The glucose level was higher in DO group when compared to the ED group (99±2 vs. 89±2 mg/dL). The DO group showed higher chronotropic response at the beginning of AES when compared to the EO group (86±4 vs. 125±8 bpm), however, the HR was similar between the groups at the other exercise intensities. At the fifth minute of the recovery, the HR was higher in the DO group when compared to the EO group (FN: 88 ± 3 vs FD: 97± 4 bpm). The AP was similar between groups during and after the AES. The results showed that young diabetic offspring presented metabolic alterations at rest, and exacerbated HR response at the beginning and in the recovery period of the AES, suggesting a higher cardiovascular risk in this population.

Treinamento físico melhora a disfunção quimiorreflexa em ratos diabéticos por estreptozotocina

O objetivo do presente estudo foi avaliar os efeitos do treinamento fisico na pressao arterial, na freq uencia cardiaca e na sensibilidade quimiorreflexa em ratos diabeticos por estreptozotocina. Os animais foram divididos em grupos controle (CS, n = 6), diabetico sedentario (DS, n = 6) e diabetico treinado (DT, n = 6). Uma semana apos a inducao do diabetes (Estreptozotocina, 50 mg/kg), ratos machos Wistar foram submetidos a um protocolo de treinamento fisico em esteira ergometrica por 10 semanas. Os sinais de pressao arterial foram gravados e processados em um sistema de aquisicao de dados (CODAS,1KHz). Cianeto de potassio (KCN,100 ug/kg) foi utilizado para avaliar a resposta bradicardica desencadeada pela estimulacao dos quimiorreceptores. A bradicardia e a hipotensao do diabetes (DS:274 ± 6 bpm e 94 ± 2 mmHg vs CS:332 ± 5 bpm e 108 ± 2 mmHg) foram atenuadas pelo treinamento fisico (DT:299 ± 5 bpm e 107 ± 2 mmHg). A resposta bradicardica foi menor nos ratos DS (33 ± 5 bpm) quando comparado aos ratos CS (182 ± 3 bpm) e DT (89 ± 10 bpm). Concluindo, o treinamento fisico reverteu a hipotensao e a bradicardia e melhorou a sensibilidade quimioreflexa em ratos STZ. Considerando que diabeticos com reflexos cardiovasculares anormais apresentam maior mortalidade que diabeticos com funcao reflexa autonomica normal, os resultados obtidos sugerem que o treinamento fisico pode contribuir para a reducao do risco cardiovascular nesta populacao devendo ser considerado no manejo do paciente diabetico