K. De Angelis

Bio: K. De Angelis is an academic researcher from University of São Paulo. The author has contributed to research in topics: Baroreflex & Blood pressure. The author has an hindex of 14, co-authored 19 publications receiving 744 citations. Previous affiliations of K. De Angelis include University of Rio Grande & Universidade Federal do Rio Grande do Sul.

Exercise training changes autonomic cardiovascular balance in mice

Abstract: Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of hear...

Effects of exercise training on autonomic and myocardial dysfunction in streptozotocin-diabetic rats.

Abstract: Several investigators have demonstrated that diabetes is associated with autonomic and myocardial dysfunction. Exercise training is an efficient non-pharmacological treatment for cardiac and metabolic diseases. The aim of the present study was to investigate the effects of exercise training on hemodynamic and autonomic diabetic dysfunction. After 1 week of diabetes induction (streptozotocin, 50 mg/kg, iv), male Wistar rats (222 ‐ 5 g, N = 18) were submitted to exercise training for 10 weeks on a treadmill. Arterial pressure signals were obtained and processed with a data acquisition system. Autonomic function and intrinsic heart rate were studied by injecting methylatropine and propranolol. Left ventricular function was assessed in hearts perfused in vitro by the Langendorff technique. Diabetes (D) bradycardia and hypotension (D: 279 ‐ 9 bpm and 91 ‐ 4 mmHg vs 315 ‐ 11 bpm and 111 ‐ 4 mmHg in controls, C) were attenuated by training (TD: 305 ‐ 7 bpm and 100 ‐ 4 mmHg). Vagal tonus was decreased in the diabetic groups and sympathetic tonus was similar in all animals. Intrinsic heart rate was lower in D (284 ‐ 11 bpm) compared to C and TD (390 ‐ 8 and 342 ‐ 14 bpm, respectively). Peak systolic pressure developed at different pressures was similar for all groups, but +dP/dt max was decreased and -dP/dt max was increased in D. In conclusion, exercise training reversed hypotension and bradycardia and improved myocardial function in diabetic rats. These changes represent an adaptive response to the demands of training, supporting a positive role of physical activity in the management of diabetes.

Cardiovascular control in experimental diabetes

Abstract: Several studies have reported impairment in cardiovascular function and control in diabetes. The studies cited in this review were carried out from a few days up to 3 months after streptozotocin administration and were concerned with the control of the circulation. We observed that early changes (5 days) in blood pressure control by different peripheral receptors were maintained for several months. Moreover, the impairment of reflex responses observed after baroreceptor and chemoreceptor stimulation was probably related to changes in the efferent limb of the reflex arc (sympathetic and parasympathetic), but changes also in the central nervous system could not be excluded. Changes in renal sympathetic nerve activity during volume expansion were blunted in streptozotocin-treated rats, indicating an adaptive natriuretic and diuretic response in the diabetic state. The improvement of diabetic cardiovascular dysfunction induced by exercise training seems to be related to changes in the autonomic nervous system. Complementary studies about the complex interaction between circulation control systems are clearly needed to adequately address the management of pathophysiological changes associated with diabetes.

Exercise Training in Aging: Hemodynamic, Metabolic, and Oxidative Stress Evaluations

Abstract: The effects of exercise training on hemodynamic and metabolic parameters as well as on responses to oxidative stress in aged individuals are controversial. The aim of the present study was to investigate changes in heart hate, mean arterial pressure, vasoreactivity, and plasma levels of insulin and glucose in male aged Wistar rats submitted to exercise training for 11 weeks (1 h/d; 5 d/wk) in a treadmill. The isolated heart was perfused by H2O2, and oxidative stress was evaluated using thiobarbituric acid reactive substances. Cardiovascular functions were recorded with a data acquisition system (CODAS, 1 kHz). Trained aged rats were bradycardic as compared with sedentary aged rats (298+/-7 versus 336+/-16 bpm) but presented similar mean arterial pressure and vasoreactivity and plasma levels of insulin and of glucose, which were quantified by radioimmunoassay and colorimetric enzymatic test. Plasma levels of insulin and of glucose ratio were increased in trained aged rats (6.9+/-0.7 versus 3.5+/-0.4 in sedentary aged rats), and the response to oxidative stress was decreased (0.4+/-0.1 versus 0.7+/-0.1 nmol/mg protein in sedentary aged rats). These results showed that exercise training produced a lower resting heart rate as well as changes in metabolic and oxidative responses. This suggests a higher myocardium protection of trained than sedentary aged rats.

Parasympathetic dysfunction is associated with insulin resistance in fructose-fed female rats

Abstract: The objective of the present study was to identify metabolic, cardiovascular and autonomic changes induced by fructose overload administered in the drinking water of rats for 8 weeks. Female Wistar rats (200-220 g) were divided into 2 groups: control (N = 8) and fructose-fed rats (N = 5; 100 mg/L fructose in drinking water for 8 weeks). The autonomic control of heart rate was evaluated by pharmacological blockade using atropine (3 mg/kg) and propranolol (4 mg/kg). The animals were submitted to an intravenous insulin tolerance test (ITT) and to blood glucose measurement. The fructose overload induced a significant increase in body weight (approximately 10%) and in fasting glycemia (approximately 28%). The rate constant of glucose disappearance (KITT) during ITT was lower in fructose-fed rats (3.25 +/- 0.7%/min) compared with controls (4.95 +/- 0.3%/min, P < 0.05) indicating insulin resistance. The fructose-fed group presented increased arterial pressure compared to controls (122 +/- 3 vs 108 +/- 1 mmHg, P < 0.05) and a reduction in vagal tonus (31 +/- 9 vs 55 +/- 5 bpm in controls, P < 0.05). No changes in sympathetic tonus were observed. A positive correlation, tested by the Pearson correlation, was demonstrable between cardiac vagal tonus and KITT (r = 0.8, P = 0.02). These data provided new information regarding the role of parasympathetic dysfunction associated with insulin resistance in the development of early metabolic and cardiovascular alterations induced by a high fructose diet.

Diabetic Cardiomyopathy: Evidence, Mechanisms, and Therapeutic Implications

Abstract: The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity) This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease

Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse.

Abstract: Cardiac fibroblasts, myocytes, endothelial cells, and vascular smooth muscle cells are the major cellular constituents of the heart. The aim of this study was to observe alterations in myocardial c...

Exercise Training for Type 2 Diabetes Mellitus Impact on Cardiovascular Risk: A Scientific Statement From the American Heart Association

Abstract: 1. Introduction …3244 2. Beneficial Effects of Exercise in T2DM…3245 3. Cardiac Risks of Exercise Training in T2DM…3249 4. Noncardiac Risks of Exercise Training in T2DM…3251 5. Exercise Training Guidelines…3252 6. Approaches to Adherence…3254 7. Special/Minority Groups…3255 8. Conclusions…3256 9. References…3257 The increasing prevalence of overweight and obesity has led to an unprecedented epidemic of type 2 diabetes mellitus (T2DM)1–4 and is likely to be followed by an epidemic of patients with complications of T2DM.5 Given the observed increases in the prevalence of T2DM in adults over the past few decades in developed countries,1,2,6 population-based efforts to reduce the cardiovascular complications of T2DM are as critical as the measures to prevent the problem.4,7 T2DM is the sixth-leading cause of death,8 with most deaths attributed to cardiovascular disease (CVD; nearly 70%) and with ischemic heart disease being responsible for nearly 50% of these deaths.9 The economic cost of T2DM has been estimated to be $172 billion in 2007 in the United States alone3 (up from $132 billion in 2002)10 and is likely to be greater when the other indirect costs of its associated complications are included.11 These complications are due to atherosclerotic vascular disease4 but also reflect a susceptibility of patients with T2DM to heart failure,12,13 perhaps mediated by direct effects on the myocardium.14,15 Pharmaceutical intervention for glycemic control has shown beneficial results for microvascular complications in patients with T2DM; however, whether this therapy has beneficial effects on macrovascular complications and …

Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment

Abstract: Diabetes mellitus is an important and prevalent risk factor for congestive heart failure. Diabetic cardiomyopathy has been defined as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause such as coronary artery disease or hypertension. The disease course consists of a hidden subclinical period, during which cellular structural insults and abnormalities lead initially to diastolic dysfunction, later to systolic dysfunction, and eventually to heart failure. Left ventricular hypertrophy, metabolic abnormalities, extracellular matrix changes, small vessel disease, cardiac autonomic neuropathy, insulin resistance, oxidative stress, and apoptosis are the most important contributors to diabetic cardiomyopathy onset and progression. Hyperglycemia is a major etiological factor in the development of diabetic cardiomyopathy. It increases the levels of free fatty acids and growth factors and causes abnormalities in substrate supply and utilization, calcium homeostasis, and lipid metabolism. Furthermore, it promotes excessive production and release of reactive oxygen species, which induces oxidative stress leading to abnormal gene expression, faulty signal transduction, and cardiomyocytes apoptosis. Stimulation of connective tissue growth factor, fibrosis, and the formation of advanced glycation end-products increase the stiffness of the diabetic hearts. Despite all the current information on diabetic cardiomyopathy, translational research is still scarce due to limited human myocardial tissue and most of our knowledge is extrapolated from animals. This paper aims to elucidate some of the molecular and cellular pathophysiologic mechanisms, structural changes, and therapeutic strategies that may help struggle against diabetic cardiomyopathy.