Effects of a multidisciplinary weight loss intervention on anaerobic and aerobic aptitudes in severely obese adolescents.

OBJECTIVE: To investigate if a multidisciplinary weight loss programme in adolescents suffering severe obesity allows an improvement of anaerobic and aerobic aptitudes. DESIGN: In all, 55 adolescents (33 girls and 22 boys) suffering from severe obesity were enrolled in an interdisciplinary weight reduction programme lasting 6-12 months. Progressive submaximal physical activity was performed and national dietary allowances for adolescents with low levels of physical activity were provided. MEASUREMENTS: Total and regional body composition and anaerobic aptitudes (handgrip strength (HGS), vertical jump height (VJH)) and aerobic aptitudes (maximal aerobic power (MAP), maximal oxygen uptake (VO(2max))) were measured before and after weight loss. RESULTS: The mean reduction of body mass index (BMI) was similar in girls (21.4+/-5.9%) and boys (23.7+/-6.4%). Fat mass (FM) steepest drop was observed in the trunk (-63.2+/-10.1% in boys and -51.5+/-11.4% in girls). The total lean mass (LM) did not vary in both sexes. Right HGS and VJH increased in both sexes (P<0.05), whereas left HGS increased only in boys. MAP and VO(2max) per kg BW increased (P< 0.0001) in both sexes (2.3+/-0.3 vs 1.7+/-0.3 W/kg and 32.8+/-4.5 vs 26.7+/-4.1 ml/min/kg in girls and 2.8+/-1.9 vs 1.9+/-0.4 W/kg and 39.1+/-6.3 vs 27.9+/-5.1 ml/min/kg in boys, respectively), whereas MAP and VO(2max) in absolute value and per kg LM increased only in boys (P=0.04). Total LM was the strongest determinant of HGS, VJH, MAP and VO(2max) in both sexes (P<0.005). CONCLUSIONS: Multidisciplinary weight reduction programme including moderate dietary restriction in combination with regular physical training induced an improvement of anaerobic and aerobic aptitudes, a marked reduction of obesity and a preservation of LM in severely obese adolescents.

Effects of a multidisciplinary weight loss intervention on body composition in obese adolescents.

OBJECTIVE: To investigate if a multidisciplinary weight loss program in adolescents suffering severe obesity allows adequate growth and development and avoid lean mass loss. DESIGN: A total of 55 adolescents (33 girls and 22 boys) suffering severe obesity were enrolled in an interdisciplinary weight reduction program lasting 6-12 months. Progressive submaximal physical activity was performed and national dietary allowances for adolescents with low levels of physical activity energy were provided. MEASUREMENTS: Total and segmental body composition was assessed by means of dual-energy X-ray absorptiometry. RESULTS: The mean height significantly increased (P<0.001). The mean body mass index (BMI) dropped in boys from 34.5+/-3.2 to 25.5+/-2.3 kg/m(2) and in girls from 38.4+/-4.1 to 28.4+/-4.1 kg/m(2). Height increased according to the expected pattern (P<0.001). Total lean mass (LM) did not vary and was positively correlated to pubertal development in both sexes before and after weight loss. Steepest drop in fat mass (FM) was observed in the trunk (-63.2+/-10.1% in boys and -51.5+/-11.4% in girls). Decrease in BMI and FM was tightly correlated in both sexes. However, slopes significantly differed (P<0.0005) so that a decrease of 1 kg/m(2) in BMI corresponded to a decrease of 3.92 kg in FM in girls and of 5.44 kg in boys. In each sex, FM at baseline and duration of the treatment were the main determinants of the decrease in FM. CONCLUSION: During adolescence, despite a major weight loss, adequate growth and preservation of LM can be achieved. Weight loss kinetics markedly differs between boys and girls. Low-calorie diets are unnecessary to achieve a marked reduction of severe obesity during puberty.

Transient involvement of endothelin in hypertrophic remodeling of small arteries.

OBJECTIVE: This study was designed to evaluate the capacity of norepinephrine (NE) to induce hypertrophic remodeling of small arteries in rats, and to determine the involvement of endothelin (ET) to initiate and maintain it. DESIGN AND RESULTS: Treatment with NE (2.5 microg/kg per min) for 14 or 28 days produced a similar inward hypertrophic remodeling, characterized by a smaller lumen, but increased media thickness and cross-sectional area. Arterial stiffness was reduced. Histological evaluation confirmed the hypertrophic nature of remodeling. Concomitant administration of LU135252 (ET-receptor antagonist) for the first 14 days of NE administration prevented the development of hypertrophy, without altering arterial mechanics. Treatment with the same antagonist from day 14 to day 28 of NE or angiotensin II (Ang II) treatment failed to regress established vascular hypertrophy. In contrast, normalization of arterial structure was observed with prazosin, an alpha-adrenergic blocker. Endothelin content in small mesenteric arteries showed a transient elevation following chronic NE administration. CONCLUSIONS: Increased circulating NE levels are associated with hypertrophic remodeling of small arteries, in which ET plays an initiating role. However, the maintenance of vascular hypertrophy is ET-independent, either in the presence of augmented circulating levels of NE or Ang II. Thus, early rather than late treatment with ET-receptor antagonists may be a preferable approach to limit small artery-mediated end-organ damage in cardiovascular diseases.

Norepinephrine-induced aortic hyperplasia and extracellular matrix deposition are endothelin-dependent.

BACKGROUND: Sympathetic hyperactivity is observed in several disease states and may contribute to cardiovascular hypertrophic remodeling. Endothelin has been suggested to be a mediator of hypertrophy. OBJECTIVE: To examine the involvement of endothelin in maintaining the growth response induced by exogenous norepinephrine. DESIGN AND METHODS: Rats were treated with norepinephrine (2.5 microg/Kg per min subcutaneously) for 2 and 4 weeks, alone or in association with the selective endothelin-A (ETA) receptor antagonist, darusentan (LU135252, 30 mg/Kg per day orally) for weeks 3 and 4. RESULTS: Increases in medial cell number and accumulation of collagen and elastin characterized norepinephrine-induced aortic remodeling. These effects occurred without marked changes of mean arterial pressure, but may be related to enhanced pressure variability in addition to direct effects of norepinephrine. Inhibition of ETA receptors by darusentan reversed aortic alterations produced by infusion of norepinephrine. Evaluation of medial apoptosis did not reveal any significant change in any group at 4 weeks. CONCLUSIONS: Antagonism of ETA receptors effectively and rapidly reversed norepinephrine-induced aortic structural and compositional changes, suggesting a central role of endothelin in mediating this response. Thus, ETA receptor antagonists may help to regress large artery remodeling in conditions of increased circulating catecholamine concentrations.

An update on the status of endothelin receptor antagonists for hypertension.

Endothelin receptor antagonists (ETRA) are actively developed by the pharmaceutical industry for several cardiovascular indications. In the context of hypertension, preclinical studies are increasingly focused on prevention or regression of end-organ damage and drug combination than on control of arterial pressure in monotherapy, as most experimental models have already been studied. In general, the antihypertensive effect of ETRA is limited but the overwhelming efficacy of this class of drugs to prevent several end-organ damages warrants judicious combination. However, the few studies looking at regression of hypertension-induced cardiovascular alterations proved less successful, suggesting that ETRA should be used early in the treatment of hypertension to obtain full benefit. Judging from the progression of ongoing trials and the development of new trials patients suffering from pulmonary hypertension and heart failure may be the first to benefit from this new class of drugs. However, it is expected that once on the market, responsive subsets of hypertensive patients will be identified and will benefit from end-organ protection.

[Role of endothelin in the hypertrophic remodeling of small arteries induced by exogenous norepinephrine]. / Rôle de l'endothéline dans le remodelage hypertrophique des petites artères induit par la norépinéphrine exogène.

In a subset of hypertensive patients, activity of the sympathetic nervous system (SNS) is enhanced. Hypertension is also associated with an adaptative process where small arteries (lumen < 300 microns) are subjected to structural changes (eutrophic or hypertrophic remodeling). Since, it has been shown that norepinephrine (NE) can induced proliferation of vascular smooth muscle cells, the purpose of the present study was to determine the effect of a chronic treatment with NE, mimicking hyperactivity of SNS, on small artery structure. The role of endothelin (ET) in the process was also evaluated. To achieve these goals, control rats were compared with rats receiving NE 2.5 micrograms/kg/min alone or in combination with LU135252 30 mg/kg/d (ET-receptor antagonist, affinity ETA/ETB approximately equal to 100) for 2 weeks. Blood pressure was measured intra-arterially in conscious rats prior to sacrifice. Geometric parameters of the basilar artery were determined in pressurized and perfused conditions with calcium free Krebs solution. Plasma NE and arterial mesenteric ET levels were determined by HPLC and RIA respectively. Blood pressured was not altered following exogenous administration of NE for 2 weeks. However, media thickness increased while the lumen diameter was reduced at the level of the basilar artery, leading to elevated media:lumen ratio (p < 0.05). This morphological alteration was associated with a significant augmentation of the basilar artery cross-sectional area (CSA). Co-administration of LU135252 with NE prevented partially the increase of M/L while the elevation of CSA was completely blunted. Plasma levels of NE were significantly and similarly elevated in groups receiving NE but, interestingly, mesenteric ET levels were not modified by any treatment. These results suggest that chronic NE administration induced an hypertrophic inward remodeling of small arteries independently from blood pressure, which required the participation of ET as an obligatory intermediate. Furthermore, the local production of ET is probably enhanced transiently in the first days of NE administration and come back to control level at 2 weeks. Thus, early therapy initiation with an ET-receptor antagonist prevents vascular remodeling in conditions of SNS hyperactivity, which may contribute to lower risks of end-organ damage.