Maria Tereza Zanella

Role of Bradykinin in Insulin Sensitivity and Blood Pressure Regulation During Hyperinsulinemia

The purpose of these experiments was to determine in normotensive rats the role of endogenous bradykinin, prostaglandins, and nitric oxide in glucose metabolism and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were treated with two different bradykinin antagonists, indomethacin or N omega-nitro-L-arginine methyl ester, concurrently with a euglycemic clamp with insulin infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma insulin levels, and insulin sensitivity index were determined over 2 hours. Bradykinin inhibition dramatically reduced glucose uptake and insulin sensitivity index during both the lower and higher insulin infusion rates to 30% and 32%, respectively, of values observed in control rats. Inhibition of prostaglandins or nitric oxide did not alter glucose metabolism in these rats. Blood pressure remained unchanged in the control group throughout the clamp but increased significantly in rats submitted to inhibition of bradykinin, prostaglandins, or nitric oxide, suggesting that these vasodilator systems tend to counteract the hypertensive effect of hyperinsulinemia. The counterregulatory component attributable to bradykinin was about twice as great as that attributable to nitric oxide. These findings suggest that insulin infusion in normotensive Wistar rats fails to raise blood pressure because its effects are offset by mobilization of vasodilator mechanisms, such as bradykinin, prostaglandins, and nitric oxide. Bradykinin seems to play the most important homeostatic role under these conditions, because its inhibition significantly reduces insulin sensitivity and allows blood pressure to rise.

Eficácia de uma intervenção psicológica no estilo de vida para redução do risco coronariano

OBJECTIVE: To evaluate the efficacy of a program of lifestyle change through psychological intervention, combined with pharmacological therapy, for coronary risk reduction in uncontrolled hypertensive patients with overweight and dyslipidemia over 11 months of follow-up. METHODS: A randomized controlled trial with 74 patients assigned to three different treatment programs. One group (CT) only received conventional pharmacological treatment. Another group (OG) received pharmacological treatment and participated in a guidance program to control cardiovascular risk factors. A third group (LSPI) received pharmacological treatment and participated in a brief psychological intervention program for reduction of estresse levels and changing of eating behavior. The main measure was the Framingham risk index. RESULTS: CT patients presented an average reduction of 18% (p = 0.001) in coronary risk; OG patients elevated the risk by 0.8% (NS) and the LSPI group showed an average reduction of 27% on the Framingham risk index (p = 0.001). CONCLUSION: Pharmacological treatment combined with psychological intervention for reduction of estresse level and changing of eating behavior resulted in additional benefits in coronary risk reduction.

TNF-α modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes

PURPOSE Systemic inflammatory conditions, as seen in obesity and in the metabolic syndrome, are associated with high plasmatic levels of proatherogenic and prothromboticadipokines and low levels of adiponectin. Inhibitors of HMG-CoA reductase have beneficial effects in reducing cardiovascular events attributed predominantly to its lipid-lowering effects and recent studies suggest that these effects might be due to its anti-inflammatory properties. Based on the pleiotropic properties of simvastatin we studied the effects of this drug on the secretion and expression of adiponectin, PAI-1 and MCP-1 in mature adipocytes under baseline conditions and after an inflammatory stimulation. MATERIALS AND METHODS The differentiated adipocytes were incubated with 10 μM simvastatin or vehicle and TNF-α 10 ng/mL or vehicle were added to treatment media. After 24h of incubation, the media was harvested and the proteins of interest were analyzed by Multiplex method. Gene expression was analyzed by real time-PCR. RESULTS The addition of TNF-α increased the expression and secretion of MCP-1 and PAI-1. However, stimulation did not interfere with the secretion of adiponectin, despite having significantly reduced its expression. Our data also demonstrated that simvastatin reduced the expression and secretion of MCP-1, under baseline (770.4 ± 199.9 vs 312.7 ± 113.7 and 1.00 ± 0.14 vs 0.63 ± 0.13, p<0.05, respectively) and inflammatory conditions (14945 ± 228.7 vs 7837.6 ± 847.4 and 24.16 ± 5.49 vs 14.97 ± 2.67, p<0.05, p<0.05, respectively). Simvastatin also attenuated the increase in expression and secretion of PAI-1 induced by TNF-α (16898.6 ± 1663.3 vs 12922.1 ± 843.9 and 5.19 ± 3.12 vs 0.59 ± 0.16, respectively p<0.05), but under baseline conditions had no effect on the expression or secretion of PAI-1. The statin increased the expression of adiponectin under baseline conditions and inflammatory stimulation (1.03 ± 0.08 vs 4.0 ± 0.96 and 0.77 ± 0.19 vs 2.16 ± 0.23, respectively, p<0.05) and also increased the secretion of this adipokine but only with the inflammatory stimulus (5347.7 ± 1789.3 vs 7327.3 ± 753.6, p<0.05). CONCLUSIONS Our findings suggested that simvastatin counteracted the stimulatory effect of TNF-α on secretion and expression of MCP-1, PAI-1 and adiponectin, implying a potential anti-atherogenic effect during the inflammatory process; these pleitropic effects were more pronounced with HMG-CoA reductase inhibitor.

Evaluation of quality of life in severely obese patients after bariatric surgery carried out in the public healthcare system

OBJECTIVES To assess QoL of obese patients in the Brazilian public healthcare system, before and after bariatric surgery, and to determine the appropriateness of the Moorehead-Ardelt Questionnaire II (M-A-QoLQII) compared with the Short-Form Health Survey (SF-36). SUBJECTS AND METHODS Forty-one severe obese patients in a waiting-list, and 84 patients who underwent bariatric surgery were included. Correlations were tested and reliability determined by the Cronbachs coefficient. RESULTS BMI differed between the pre- and post-surgery groups (52.3 ± 8.3 kg/m(2) vs. 32.5 ± 6.4 kg/m(2), p < 0.001). The latter showed better scores in the SF-36 domains than in the pre-surgery. SF-36 and M-A-QoLQII categories were correlated (r = 0.53, 0.49 and 0.47, for vitality, mental health, and general health domains, p < 0.001). In the logistic regression, age, previous BMI, and loss of excess weight were associated with functional capacity. CONCLUSIONS The outcomes of bariatric surgery obtained in a Brazilian public healthcare center were successful. M-A-QoLII represents a useful tool to assess surgery outcomes, including QoL.

Diabetes and cardiovascular disease: from evidence to clinical practice – position statement 2014 of Brazilian Diabetes Society

There is a very well known correlation between diabetes and cardiovascular disease but many health care professionals are just concerned with glycemic control, ignoring the paramount importance of controlling other risk factors involved in the pathogenesis of serious cardiovascular diseases. This Position Statement from the Brazilian Diabetes Society was developed to promote increased awareness in relation to six crucial topics dealing with diabetes and cardiovascular disease: Glicemic Control, Cardiovascular Risk Stratification and Screening Coronary Artery Disease, Treatment of Dyslipidemia, Hypertension, Antiplatelet Therapy and Myocardial Revascularization. The issue of what would be the best algorithm for the use of statins in diabetic patients received a special attention and a new Brazilian algorithm was developed by our editorial committee. This document contains 38 recommendations which were classified by their levels of evidence (A, B, C and D). The Editorial Committee included 22 specialists with recognized expertise in diabetes and cardiology.

Left Ventricular Hypertrophy Evaluation in Obese Hypertensive Patients: Effect of Left Ventricular Mass Index Criteria

PURPOSE To evaluate left ventricular mass (LVM) index in hypertensive and normotensive obese individuals. METHODS Using M mode echocardiography, 544 essential hypertensive and 106 normotensive patients were evaluated, and LVM was indexed for body surface area (LVM/BSA) and for height2 (LVM/h2). The 2 indexes were then compared in both populations, in subgroups stratified according to body mass index (BMI): <27; 27-30; >/= 30kg/m2. RESULTS The BSA index does not allow identification of significant differences between BMI subgroups. Indexing by height2 provides significantly increased values for high BMI subgroups in normotensive and hypertensive populations. CONCLUSION Left ventricular hypertrophy (LVH) has been underestimated in the obese with the use of LVM/BSA because this index considers obesity as a physiological variable. Indexing by height2 allows differences between BMI subgroups to become apparent and seems to be more appropriate for detecting LVH in obese populations.

Left Ventricular Diastolic Function in Essential Hypertensive Patients. Influence of Age and Left Ventricular Geometry

PURPOSE To evaluate diastolic dysfunction (DD) in essential hypertension and the influence of age and cardiac geometry on this parameter. METHODS Four hundred sixty essential hypertensive patients (HT) underwent Doppler echocardiography to obtain E/A wave ratio (E/A), atrial deceleration time (ADT), and isovolumetric relaxation time (IRT). All patients were grouped according to cardiac geometric patterns (NG - normal geometry; CR - concentric remodeling; CH- concentric hypertrophy; EH - eccentric hypertrophy) and to age (<40; 40 - 60; >60 years). One hundred six normotensives (NT) persons were also evaluated. RESULTS A worsening of diastolic function in the HT compared with the NT, including HT with NG (E/A: NT - 1.38+/-0.03 vs HT - 1.27+/-0.02, p<0.01), was observed. A higher prevalence of DD occurred parallel to age and cardiac geometry also in the prehypertrophic groups (CR). Multiple regression analysis identified age as the most important predictor of DD (r2=0.30, p<0.01). CONCLUSION DD was prevalent in this hypertensive population, being highly affected by age and less by heart structural parameters. DD is observed in incipient stages of hypertensive heart disease, and thus its early detection may help in the risk stratification of hypertensive patients.

Cross-sectional Study on Blood Pressure Control in the Department of Nephrology of the Escola Paulista de Medicina - UNIFESP

OBJECTIVE To assess hypertension control rates in a specialized university-affiliated medical department, the influence of sex, diabetes, and obesity on that control, and the strategies for the treatment of hypertension. METHODS We carried out a cross-sectional study with 1,210 patients followed up for at least 6 months. Information was gathered from medical and nursing records and comprised the following data: sex, age, weight, height, abdominal and hip circumferences, blood pressure, and class and number of the antihypertensive drugs prescribed. To assess obesity, we used body mass index and waist/hip ratio. Blood pressure was considered under control when its levels were below 140/90 mmHg. RESULTS The study consisted of 73% females and 27% males. Most females (31.7%) were 50 to 59 years of age, and most males (28.3%) were 60 to 69 years. The blood pressure control rate found was 20.9% for the 1,210 patients and 23.4% for the hypertensive diabetic patients (n=290). Despite the low control rates found, 70% of the patients used 1 or 2 antihypertensive medications. A high prevalence of obesity (38%) was observed, and females had a greater abdominal obesity index than males did (90% vs 82%, p<0.05). Patients with a greater body mass index had less control of blood pressure. CONCLUSION The percentage of hypertensive patients with controlled blood pressure levels was low and was associated with a high prevalence of obesity. These data indicate the need for reviewing the strategies of global treatment for hypertension.

Blood pressure and cardiorenal responses to antihypertensive therapy in obese women

OBJECTIVE Blood pressure (BP) and target organ responses to antihypertensive drugs are not well established in hypertensive obese patients. This study is aimed at evaluating the effects of obesity and adiposity distribution patterns on these responses. METHODS 49 hypertensive obese women were designated to different groups according to waist to hip ratio measurements--37 with troncular and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine combination therapy to achieve a BP lower than 140/90 mmHg. Ambulatory blood pressure monitoring (ABPM), echocardiography, and albuminuria were assessed before and after the intervention. RESULTS After 24 weeks, weight loss was less than 2% in both groups. ABPM targets were achieved in 81.5% of patients upon a combination of 2(26.5%) or 3(55.1%) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity)/-23.6/-14.9 mmHg (peripheral obesity) were obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients. Upon BP control, microalbuminuria was markedly decreased, while only slight decrease in left ventricular mass was observed for both groups. CONCLUSIONS In the absence of weight loss, most patients required combined antihypertensive therapy to control their BP, regardless of their body fat distribution pattern. Optimal target BP and normal albuminuria were achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude.

Cardiovascular Effects of a Specific Nonpeptide Antagonist of Substance P (NK-1) Receptor in DOCA-Salt Hypertension

The neurotransmitter substance P acts also as a potent vasodilator. Its participation in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt hypertension was evaluated by an acute infusion of a newly synthesized, potent, specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP 96,345. In conscious unrestrained rats, CP 96,345 induced significant and sustained increases in mean arterial pressure of DOCA-salt rats but only small, transient, and nonsignificant rises in blood pressure of sham-treated control rats. The rise in blood pressure was not accompanied by changes in heart rate. Maximal blood pressure increase in DOCA-salt rats was 31.7 +/- 14.8 mm Hg. In a second series of experiments, the hemodynamic effects of this antagonist were evaluated under anesthesia in both DOCA-salt and sham-treated control rats by the thermodilution method. During CP 96,345 infusion, sustained increases in cardiac index and stroke volume and decreases in total peripheral resistance were observed in both DOCA-salt and control rats. In DOCA-salt rats, cardiac index rose by 79.4%, while total peripheral resistance fell by 27.9% of the baseline values. In control rats, the changes were smaller (+27.2% and -22.5%, respectively). Stroke volume changed in parallel to cardiac output in both groups. The data suggest that acute blockade of NK-1 receptors increases blood pressure in DOCA-salt rats mainly by an increase in cardiac output. We conclude that endogenous substance P tends to counteract the DOCA-salt-induced elevation of blood pressure by modulating both cardiac output and peripheral resistance.