Treatment of Obese Adolescents: The Influence of Periodization Models and ACE Genotype

The aims of the present study were to compare the effects of two periodization models on metabolic syndrome risk factors in obese adolescents and verify whether the angiotensin-converting enzyme (ACE) genotype is important in establishing these effects. A total of 32 postpuberty obese adolescents were submitted to aerobic training (AT) and resistance training (RT) for 14 weeks. The subjects were divided into linear periodization (LP, n = 16) or daily undulating periodization (DUP, n = 16). Body composition, visceral and subcutaneous fat, glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles, blood pressure, maximal oxygen consumption (VO(2max)), resting metabolic rate (RMR), muscular endurance were analyzed at baseline and after intervention. Both groups demonstrated a significant reduction in body mass, BMI, body fat, visceral and subcutaneous fat, total and low-density lipoprotein cholesterol, blood pressure and an increase in fat-free mass, VO(2max), and muscular endurance. However, only DUP promoted a reduction in insulin concentrations and HOMA-IR. It is important to emphasize that there was no statics difference between LP and DUP groups; however, it appears that there may be bigger changes in the DUP than LP group in some of the metabolic syndrome risk factors in obese adolescents with regard to the effect size (ES). Both periodization models presented a large effect on muscular endurance. Despite the limitation of sample size, our results suggested that the ACE genotype may influence the functional and metabolic characteristics of obese adolescents and may be considered in the future strategies for massive obesity control.

Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice

Lacchini S, Heimann AS, Evangelista FS, Cardoso L, Silva GJ, Krieger JE. Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice. Physiol Genomics 37: 225-230, 2009. First published March 3, 2009; doi:10.1152/physiolgenomics.90288.2008.-We tested the hypothesis that small changes in angiotensin I-converting enzyme (ACE) expression can alter the vascular response to injury. Male mice containing one, two, three, and four copies of the Ace gene with no detectable vascular abnormality or changes in blood pressure were submitted to cuff-induced femoral artery injury. Femoral thickening was higher in 3- and 4-copy mice (42.4 +/- 4.3% and 45.7 +/- 6.5%, respectively) compared with 1- and 2-copy mice (8.3 +/- 1.3% and 8.5 +/- 0.9%, respectively). Femoral ACE levels from control and injured vessels were assessed in 1- and 3-copy Ace mice, which represent the extremes of the observed response. ACE vascular activity was higher in 3- vs. 1-copy Ace mice (2.4-fold, P < 0.05) in the control uninjured vessel. Upon injury, ACE activity significantly increased in both groups [2.41-fold and 2.14-fold (P < 0.05) for 1- and 3-copy groups, respectively] but reached higher levels in 3- vs. 1-copy Ace mice (P < 0.05). Pharmacological interventions were then used as a counterproof and to indirectly assess the role of angiotensin II (ANG II) on this response. Interestingly, ACE inhibition (enalapril) and ANG II AT(1) receptor blocker (losartan) reduced intima thickening in 3-copy mice to 1-copy mouse values (P < 0.05) while ANG II treatment significantly increased intima thickening in 1-copy mice to 3-copy mouse levels (P < 0.05). Together, these data indicate that small physiologically relevant changes in ACE, not associated with basal vascular abnormalities or blood pressure levels, do influence the magnitude of cuff-induced neointima thickening in mice.

Anabolic steroid associated to physical training induces deleterious cardiac effects

DO CARMO, E. C., T. FERNANDES, D. KOIKE, N. D. DA SILVA JR., K. C. MATTOS, K. T. ROSA, D. BARRETTI, S. F. S. MELO, R. B. WICHI, M. C. C. IRIGOYEN, and E. M. DE OLIVEIRA. Anabolic Steroid Associated to Physical Training Induces Deleterious Cardiac Effects. Med. Sci. Sports Exerc., Vol. 43, No. 10, pp. 1836-1848, 2011. Purpose: Cardiac aldosterone might be involved in the deleterious effects of nandrolone decanoate (ND) on the heart. Therefore, we investigated the involvement of cardiac aldosterone, by the pharmacological block of AT1 or mineralocorticoid receptors, on cardiac hypertrophy and fibrosis. Methods: Male Wistar rats were randomized into eight groups (n = 14 per group): Control (C), nandrolone decanoate (ND), trained (T), trained ND (TND), ND + losartan (ND + L), trained ND + losartan (TND + L), ND + spironolactone (ND + S), and trained ND + spironolactone (TND + S). ND (10 mg.kg(-1).wk(-1)) was administered during 10 wk of swimming training (five times per week). Losartan (20 mg.kg(-1).d(-1)) and spironolactone (10 mg.kg(-1).d(-1)) were administered in drinking water. Results: Cardiac hypertrophy was increased 10% by using ND and 17% by ND plus training (P < 0.05). In both groups, there was an increase in the collagen volumetric fraction (CVF) and cardiac collagen type III expression (P < 0.05). The ND treatment increased left ventricle-angiotensin-converting enzyme I activity, AT1 receptor expression, aldosterone synthase (CYP11B2), and 11-beta hydroxysteroid dehydrogenase 2 (11 beta-HSD2) gene expression and inflammatory markers, TGF beta and osteopontin. Both losartan and spironolactone inhibited the increase of CVF and collagen type III. In addition, both treatments inhibited the increase in left ventricle-angiotensin-converting enzyme I activity, CYP11B2, 11 beta-HSD2, TGF beta, and osteopontin induced by the ND treatment. Conclusions: We believe this is the first study to show the effects of ND on cardiac aldosterone. Our results suggest that these effects may be associated to TGF beta and osteopontin. Thus, we conclude that the cardiac aldosterone has an important role on the deleterious effects on the heart induced by ND.

Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice

The role of exercise training (ET) on cardiac renin-angiotensin system (RAS) was investigated in 3-5 month-old mice lacking alpha(2A-) and alpha(2C-)adrenoceptors (alpha(2A)/alpha(2C)ARKO) that present heart failure (HF) and wild type control (WT). ET consisted of 8-week running sessions of 60 min, 5 days/week. In addition, exercise tolerance, cardiac structural and function analysis were made. At 3 months, fractional shortening and exercise tolerance were similar between groups. At 5 months, alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction and fibrosis associated with increased cardiac angiotensin (Ang) II levels (2.9-fold) and increased local angiotensin-converting enzyme activity (ACE 18%). ET decreased alpha(2A)/alpha(2C)ARKO cardiac Ang II levels and ACE activity to age-matched untrained WT mice levels while increased ACE2 expression and prevented exercise intolerance and ventricular dysfunction with little impact on cardiac remodeling. Altogether, these data provide evidence that reduced cardiac RAS explains, at least in part, the beneficial effects of ET on cardiac function in a genetic model of HF.

Low nanomolar concentration of mercury chloride increases vascular reactivity to phenylephrine and local angiotensin production in rats

Exposure to mercury at nanomolar level affects cardiac function but its effects on vascular reactivity have yet to be investigated. Pressor responses to phenylephrine (PHE) were investigated in perfused rat tail arteries before and after treatment with 6 nM HgCl2 during 1 h,,in the presence (E+) and absence (E-) of endothelium, after L-NAME (10(-4) M), indomethacin (10(-5) M), enalaprilate (1 mu M), tempol (1 mu M) and deferoxamine (300 mu M) treatments. HgCl2 increased sensitivity (pD(2)) without modifying the maximum response (Em) to PHE, but the pD(2) increase was abolished after endothelial damage. L-NAME treatment increased pD(2) and Emax. However, in the presence of HgCl2, this increase was smaller, and it did not modify Emax. After indomethacin treatment, the increase of pD(2) induced by HgCl2 was maintained. Enalaprilate, tempol and deferoxamine reversed the increase of pD(2) evoked by HgCl2. HgCl2 increased the angiotensin converting enzyme (ACE) activity explaining the result obtained with enalaprilate. Results suggest that at nanomolar concentrations HgCl2 increase the vascular reactivity to PHE. This response is endothelium mediated and involves the reduction of NO bioavailability and the action of reactive oxygen species. The local ACE participates in mercury actions and depends on the angiotensin 11 generation. (c) 2007 Elsevier Inc. All rights reserved.

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C) ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Baroreflex sensitivity is disturbed in many people with cardiovascular diseases such as hypertension. Brain deficiency of nitric oxide (NO), which is synthesized by NO synthase (NOS) in the citrulline-NO cycle (with argininosuccinate synthase (ASS) activity being the rate-limiting step), contributes to impaired baroreflex. We recently showed that a decapeptide isolated from Bothrops jararaca snake venom, denoted Bj-PRO-10c, exerts powerful and sustained antihypertensive activity. Bj-PRO-10c promoted vasodilatation dependent on the positive modulation of ASS activity and NO production in the endothelium, and also acted on the central nervous system, inducing the release of GABA and glutamate, two important neurotransmitters in the regulation of autonomic systems. We evaluated baroreflex function using the regression line obtained by the best-fit points of measured heart rate (HR) and mean arterial pressure (MAP) data from spontaneously hypertensive rats (SHRs) treated with Bj-PRO-10c. We also investigated molecular mechanisms involved in this effect, both in vitro and in vivo. Bj-PRO-10c mediated an increase in baroreflex sensitivity and a decrease in MAP and HR. The effects exerted by the peptide include an increase in the gene expression of endothelial NOS and ASS. Bj-PRO-10c-induced NO production depended on intracellular calcium fluxes and the activation of a G(i/o)-protein-coupled metabotropic receptor. Bj-PRO-10c induced NO production and the gene expression of ASS and endothelial NOS in the brains of SHRs, thereby improving baroreflex sensitivity. Bj-PRO-10c may reveal novel approaches for treating diseases with impaired baroreflex function. Hypertension Research (2010) 33, 1283-1288; doi: 10.1038/hr.2010.208

EVALUATION OF RED CURRANTS (RIBES RUBRUM L.), BLACK CURRANTS (RIBES NIGRUM L.), RED AND GREEN GOOSEBERRIES (RIBES UVA-CRISPA) FOR POTENTIAL MANAGEMENT OF TYPE 2 DIABETES AND HYPERTENSION USING IN VITRO MODELS

Red currants (Ribes rubrum L.), black currants (Ribes nigrum L.), red and green gooseberries (Ribes uva-crispa) were evaluated for the total phenolics, antioxidant capacity based on 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay and functionality such as in vitro inhibition of alpha-amylase, alpha-glucosidase and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension. The total phenolics content ranged from 3.2 (green gooseberries) to 13.5 (black currants) mg/g fruit fresh weight. No correlation was found between total phenolics and antioxidant activity. The major phenolic compounds were quercetin derivatives (black currants and green gooseberries) and chlorogenic acid (red currants and red gooseberries). Red currants had the highest alpha-glucosidase, alpha-amylase and ACE inhibitory activities. Therefore red currants could be good dietary sources with potential antidiabetes and antihypertension functionality to compliment overall dietary management of early stages of type 2 diabetes.

EFFECT OF THERMAL TREATMENT ON PHENOLIC COMPOUNDS AND FUNCTIONALITY LINKED TO TYPE 2 DIABETES AND HYPERTENSION MANAGEMENT OF PERUVIAN AND BRAZILIAN BEAN CULTIVARS (PHASEOLUS VULGARIS L.) USING IN VITRO METHODS

The effect of thermal treatment on phenolic compounds and type 2 diabetes functionality linked to alpha-glucosidase and alpha-amylase inhibition and hypertension relevant angiotensin I-converting enzyme (ACE) inhibition were investigated in selected bean (Phaseolus vulgaris L,) cultivars from Peru and Brazil using in vitro models. Thermal processing by autoclaving decreased the total phenolic content in all cultivars, whereas the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity-linked antioxidant activity increased among Peruvian cultivars, alpha-Amylase and alpha-glucosidase inhibitory activities were reduced significantly after heat treatment (73-94% and 8-52%, respectively), whereas ACE inhibitory activity was enhanced (9-15%). Specific phenolic acids such as chlorogenic and caffeic acid increased moderately following thermal treatment (2-16% and 5-35%, respectively). No correlation was found between phenolic contents and functionality associated to antidiabetes and antihypertension potential, indicating that non phenolic compounds may be involved. Thermally processed bean cultivars are interesting sources of phenolic acids linked to high antioxidant activity and show potential for hypertension prevention.

Potential of Ginkgo biloba L. leaves in the management of hyperglycemia and hypertension using in vitro models

Leaves from four different Ginkgo biloba L. trees (1 and 2 - females; 3 and 4 - males), grown at the same conditions, were collected during a period of 5 months (from June to October, 2007). Water and 12% ethanol extracts were analyzed for total phenolics content, antioxidant activity, phenolic profile, and the potential in vitro inhibitory effects on alpha-amylase, alpha-glucosidase, and Angiotensin I-Converting Enzyme (ACE) enzymes related to the management of diabetes and hypertension. The results indicated a significant difference among the trees in all functional benefits evaluated in the leaf extracts and also found important seasonal variation related to the same functional parameters. In general, the aqueous extracts had higher total phenolic content than the ethanolic extracts. Also, no correlation was found between total phenolics and antioxidant activity. In relation to the ACE inhibition, only ethanolic extracts had inhibitory activity. (C) 2009 Elsevier Ltd. All rights reserved.

Functionality of bioactive compounds in Brazilian strawberry (Fragaria x ananassa Duch.) cultivars: Evaluation of hyperglycemia and hypertension potential using in vitro models

Fruits of seven fully ripened strawberry cultivars grown in Brazil (Dover, Camp Dover, Camarosa, Sweet Charlie, Toyonoka, Oso Grande, and Piedade) were evaluated for total phenolics, antioxidant activity based on DPPH radical scavenging assay, and functionality such as inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potentially managing hyperglycemia and hypertension. The total phenolics content ranged from 966 to 1571 mu g of gallic acid/g of fruit fresh weight for Toyonoka and Dover, respectively. No correlation was found between total phenolics and antioxidant activity. The major phenolic compounds in aqueous extracts of strawberries were ellagic acid, quercetin, and chlorogenic acid. Strawberries had high alpha-glucosidase inhibitory activity. However, alpha-amylase inhibitory activity was very low in all cultivars. This suggested that strawberries could be considered as a potential dietary source with anti-hyperglycemic potential. The evaluated cultivars had no significant ACE inhibitory activity, reflecting low anti-hypertensive potential.

Isolation and Characterization of a Natriuretic Peptide from Crotalus oreganus abyssus (Grand Canyon Rattlesnake) and its Effects on Systemic Blood Pressure and Nitrite Levels

Studies on the therapeutic potential of venom peptides have significantly advanced the development of new peptide drugs. A good example is captopril, a synthetic peptide drug, which acts as an anti-hypertensive and potentiating bradykinin, inhibiting the angiotensin-converting enzyme, whose precursor was isolated from the venom of Bothrops jararacussu. The natriuretic peptide (NPs) family comprises three members, ANP (atrial natriuretic peptide), BNP (B-type natriuretic peptide) and CNP (C-type natriuretic peptide), and has an important role in blood pressure regulation and electrolyte homeostasis. In this study, we describe, for the first time, the isolation and characterization of a novel natriuretic-like peptide (Coa_NP), isolated from Crotalus Oreganus abyssus venom. The peptide has 32 amino acids and its complete sequence is SKRLSNGCFGLKLDRIGAMSGLGCWRLINESK. The Coa_NP has an average molecular mass of 3510.98 Da and its amino acid sequence presents the loop region that is characteristic of natriuretic peptides (17 amino acids, NP domain consensus; CFGXXXDRIXXXSGLGC). Coa_NP is a natriuretic peptide of the ANP/BNP-like family, since the carboxy terminal region of CNP has its own NP domain. The functional experiments showed that Coa_NP produced biological effects similar to those of the other natriuretic peptides: (1) a dose-dependent decrease in mean arterial pressure; (2) significant increases in plasma nitrite levels, and (3) vasorelaxation in thoracic aortic rings that were pre-contracted with phenylephrine. The structural and biological aspects confirm Coa_NP as a natriuretic peptide isolated from snake venom, thus expanding the diversification of venom components.

Crotalus durissus collilineatus venom gland transcriptome: Analysis of gene expression profile

Crotalus durissus rattlesnakes are responsible for the most lethal cases of snakebites in Brazil. Crotalus durissus collilineatus subspecies is related to a great number of accidents in Southeast and Central West regions, but few studies on its venom composition have been carried out to date. In an attempt to describe the transcriptional profile of the C. durissus collilineatus venom gland, we generated a cDNA library and the sequences obtained could be identified by similarity searches on existing databases. Out of 673 expressed sequence tags (ESTs) 489 produced readable sequences comprising 201 singletons and 47 clusters of two or more ESTs. One hundred and fifty reads (60.5%) produced significant hits to known sequences. The results showed a predominance of toxin-coding ESTs instead of transcripts coding for proteins involved in all cellular functions. The most frequent toxin was crotoxin, comprising 88% of toxin-coding sequences. Crotoxin B, a basic phospholipase A(2) (PLA(2)) subunit of crotoxin, was represented in more variable forms comparing to the non-enzymatic subunit (crotoxin A), and most sequences coding this molecule were identified as CB1 isoform from Crotalus durissus terrificus venom. Four percent of toxin-related sequences in this study were identified as growth factors, comprising five sequences for vascular endothelial growth factor (VEGF) and one for nerve growth factor (NGF) that showed 100% of identity with C. durissus terrificus NGF. We also identified two clusters for metalloprotease from PII class comprising 3% of the toxins, and two for serine proteases, including gyroxin (2.5%). The remaining 2.5% of toxin-coding ESTs represent singletons identified as homologue sequences to cardiotoxin, convulxin, angiotensin-converting enzyme inhibitor and C-type natriuretic peptide, Ohanin, crotamin and PLA(2) inhibitor. These results allowed the identification of the most common classes of toxins in C. durissus collilineatus snake venom, also showing some unknown classes for this subspecies and even for C. durissus species, such as cardiotoxins and VEGF. (C) 2009 Published by Elsevier Masson SAS.

Changing patterns of coronary heart disease in the hunter region of New South Wales, Australia

A population-based observational study of men acid women aged 35-69 years in the Hunter Region of New South Wales, Australia, was conducted to assess the impact. of risk-factor modification and increased drug therapy on the trends in major coronary events and case fatality. From 1985 to 1993, there were 3006 coronary deaths and 6450 nonfatal major coronary events. Rates of death and nonfatal myocardial infarction declined, but there was an increase in hospital admissions for prolonged chess pain. Reductions in cigarette smoking, diastolic blood pressure, total cholesterol, and increased use of aspirin can fully explain the 3.3% (95% confidence interval [CI] 2.4, 4.2) average annual reduction in rates of major coronary events for men and the 4.1% (95% CI 2.7, 5.5) reduction for women. In contrast, increased use of aspirin, beta-blockers, fibrinolytic therapy, and angiotensin-converting enzyme inhibitors explain less than hall of the 8.9% (95% CI 5.9, 11.8) and 6.9% (95% CI 2.7, 10.9) average annual reduction in case fatality in hospital for men and women, respectively. These trends suggest a decline in severity of coronary heart disease consistent with reductions in risk-factor levels and improved acute medical treatment. J CLIN EPIDEMIOL 52;8:761-771, 1999. (C) 1999 Elsevier Science Inc.