0012: Cardiac effects of a treatment with prolyl-hydroxylase inhibitors (PHI), used to improve exercise performance, in sedentary and trained rats

Stabilization of the Hypoxia Inducible Factor (HIF) using prolyl-hydroxylase inhibitors (PHI) leads to an EPO synthesis which is suspected to be used as a doping practice. Such a treatment is suspected to improve endurance performance by increasing oxygen transport. However the effects of a PHI treatment on heart morphology and function has never been investigated. Therefore the aim of this study was to evaluate whether potential effects of PHI on cardiac function could contribute to explain its beneficial effect on aerobic performance.We tested the effects of a 1 week treatment with a PHI (DMOG, 150mg.kg–1, I.P.) or a placebo (NaCl) on both sedentary (Sed) and trained rats (Ex; trained during 5 weeks before treatment started; 40min at 25m.min–1 per day; 5days/week). Our first result was that PHI increased running performance (+12%, p<0,05) in both Sed and Ex groups. This increased performance was associated with a major increase in total hemoglobin in PHI-treated animals (+13% p<0,05). However, regarding cardiac function and cardiac remodeling no beneficial effect of PHI was observed. Indeed, in hearts of sedentary as well as exercised rats no significal change in any morphological parameters (LVEDs, LVEDd, AWTd, PWTd and RWT) was found. Moreover, no change in systolic function likely to explain enhanced exercise performance was observed in PHI-treated hearts, when evaluated by intraventricular pressure probe (Millar®). Finally it is interesting to note that in sedentary rat hearts an impairment of diastolic function characterized by an altered E/A and dp/dtmin ratios was found when they were challenged with isoproterenol (0,5mg.kg-1). These last results obtained in sedentary hearts could suggest that a more prolonged treatment with such PHI could have deleterious consequences on heart health and point out the danger of such a doping strategy; however, this point remains to be more precisely investigated

Long-term effects of high intensity resistance and endurance exercise on plasma leptin and ghrelin in overweight individuals:the RESOLVE Study

International audienceThe objective of this study was to evaluate the effects of high-intensity resistance and endurance exercise on body composition and plasma leptin and ghrelin concentrations in overweight individuals. One hundred participants were randomly assigned to 3 exercise interventions: high-resistance–low-aerobic exercise (Re), low-resistance–high-aerobic exercise (rE), low-resistance–low-aerobic exercise (re). Interventions began with 3 weeks of residential supervision (phase 1) after which participants had to manage the physical activity programs individually (phase 2). Body composition and plasma variables were measured at baseline and after phase 1 as well as after 3, 6, and 12 months. Significant decreases in body weight and fat were observed after phase 1 (p < 0.001) and continued at a lower rate for up to 3 months and then remained stable for the rest of the protocol. Once a body weight plateau was reached, body fat loss after the Re and rE conditions exceeded the fat loss observed in the re condition by 1.5–2 kg (p < 0.05). Leptin was significantly decreased after day 21 and month 3 (p < 0.001) and remained stable for the rest of the study. Ghrelin was significantly increased after day 21 and month 3 (p < 0.001) and returned to a level comparable to baseline between month 6 and 12 when body weight and fat had reached a plateau. In conclusion, this study reinforces the idea that an increase in exercise intensity may accentuate body fat loss before the occurrence of a body weight plateau. Resistance to further fat loss was accompanied by a decrease in plasma leptin and an increase in plasma ghrelin

Cinétique de VO2 à l'exercice modéré et intense (influences de l'entraînement et des conditions environnementales)

ORLEANS-BU Sciences (452342104) / SudocSudocFranceF

Limitation de l'hypertension artérielle pulmonaire par l'exercice physique chronique chez le rat (implication du métabolisme de la L-arginine)

L'hypertension artérielle pulmonaire (HTAP) est une pathologie des artères pulmonaires où l'élévation progressive de la pression artérielle et de la résistance circulatoire aboutit à un remodelage de la paroi vasculaire et une défaillance cardiaque droite. L'HTAP est caractérisée par une altération de la relaxation artérielle pulmonaire induite par une moindre production de monoxyde d'azote (NO), impliquant à un des niveaux de régulation, le métabolisme de la L-arginine. alors que l'exercice physique chronique, qui potentialise la vasorelaxation médiée par le NO, est largement utilisé dans l'approche thérapeutique de nombreuses maladies cardio-vasculaires, il ne fait pas partie de l'approche thérapeutique classique de l'HTAP. Nous avons émis l'hypothèse que l'exercice physique en endurance, associé à une supplémentation en L-arginine, pourrait limiter l'HTAP induite par l'hypoxie, les effets de l'exercice physique chronique aérobie par l'étude in-vivo de la pression artérielle pulmonaire et ex-vivo des propriétés vasomotrices d'anneaux isolés d'artère pulmonaire. La pression artérielle pulmonaire des rats HTAP entraînés était 18% inférieure à celle des rats non entraînés. Les anneaux d'artère pulmonaire des rats HTAP montraient une altération de la vasorelaxation et une potentialisation des propriétés de vasoconstriction, notamment par altération de la libération endothéliale de NO et diminution de la sensibilité du muscle lisse au NO. L'addition de L-arginine améliorait la vasorelaxation des artères de rats HTAP entraînés mais non des rats HTAP sédentaires, suggérant une altération de la biodisponiblité et/ou de l'utilisation de la L-arginine.Ces résultats pourraient avoir une implication importante pour le traitement de l'HTAP en suggérant l'intérêt de combiner exercice et supplémentation en L-argininePulmonary hypertension (PHT) involves pulmonary arteries with progressively increasing blood pressure and circulatory resistance leading to remodelling of pulmonary vessel wall and right heart failure. Impairment of vasorelaxation properties due to reduced nitric-oxide production through L-arginine plays a major role in the pathogeny of this disease. Exercise training is beneficial for the treatment and prevention of cardiovascular diseases, notably by potentiating of nitric oxide pathway. Surprisingly, very few clinical studies incorporated exercise sessions into the therapy of patients with PHT, we hypothesized that combining exercise training and L-arginine supplementation would limit PHT by potentiating nitric oxid-related relaxation. Therefore, we investigated the effect of chronic aerobic exercise training in rats with hypoxia-induced PHT, by measuring in vivo pulmonary artery blood pressure and ex-vivo the vasomotor properties of isolated pulmonary arterial rings. Pulmonary arterial pressure was 18% lower in exercise-trained than in sedentary PHT rats. Pulmonary artery rings of PHT rats showed impaired vasorelaxation and potentiated vasoconstriction with depressed NO production and decreased smooth muscle cell sensibilité to NO. L-arginine addition to th organ bath improved vasorelaxation in pulmonary artery rings of PHT trained but not of untrained rats, pointing to the involment of reduced L-arginine use and/or bioavailability in the endothelial dysfunction. These results might be clinically relevant for the treatment of PHT as synergistic effects of chronic exercise and L-arginine supplementation might be expectedAVIGNON-BU Centrale (840072102) / SudocSudocFranceF

Enhanced Conduit Artery Flow-Mediated Dilation in Elite Atheletes: False or Reality?

International audienc

Pollution de type urbaine au monoxyde de carbone et sensibilité du myocarde au syndrome d'ischémie-reperfusion (rôle cardioprotecteur de l'exercice)

Diverses études épidémiologiques ont mis en évidence une relation étroite entre pollution urbaine au monoxyde de carbone (CO) et mortalité cardiovasculaire. Récemment il a été mis en évidence, chez le rat, qu'une exposition prolongée à ce polluant urbain avait pour conséquence le développement d'un phénotype cellulaire pathologique, pouvant influencer la vulnérabilité du coeur à un stress aigu. L'objectif de nos travaux était donc i) d'évaluer l'impact de la pollution au CO, sur la sensibilité du myocarde de rats au syndrome d'ischémie-reperfusion (IR) ; et ii) d'évaluer les effets potentiellement cardioprotecteurs d'un exercice pratiqué régulièrement à intensité modérée, sur le remodelage phénotypique cellulaire myocardique. Pour cela, 187 rats Wistar ont été séparés en 3 groupes : des rats contrôles, des rats exposés pendant 4 semaines au CO (30-100 ppm), et des rats entraînés en endurance avant d'être exposés au CO. La sensibilité à l'IR était évaluée par ischémie régionale réalisée sur modèle de coeur isolé perfusé de Langendorff. La fonction et les mouvements calciques de cardiomyocytes isolés était évalués en condition basale et consécutivement à un protocole d'anoxie-réoxygénation. Les résultats de ce travail confirment l'apparition d un phénotype pathologique chez les rats exposés de façon prolongée au CO. Ce phénotype pathologique caractérisé dans notre travail par une altération de l homéostasie calcique et du statut redox cellulaire ainsi qu'une expression tissulaire de iNOS apparait comme à l'origine de la plus grande vulnérabilité du coeur à un stress d IR. Un autre résultat majeur de ce travail est qu une stratégie de cardioprotection par un exercice d'intensité modérée pratiqué de manière régulière, permet de prévenir le remodelage pathologique cardiomyocytaire et ainsi l'augmentation de la sensibilité du myocarde à l'IREpidemiological studies suggested that carbon monoxide (CO) urban air pollution is mainly related to cardiovascular mortality. In addition, recent experimental studies have highlighted that CO exposure was responsible for the development of cardiomyocytes pathological remodeling, which can render the heart more vulnerable to acute stresses. Therefore, the aim of this experimental work was to i) evaluate the impact of prolonged exposure to simulated CO urban pollution on the sensitivity of the myocardium to IR ; and ii) evaluate potential cardioprotective effects of regular bouts of endurance training in this model. 187 Wistar rats were separated into 3 groups : control rats, CO rats exposed during 4 weeks to CO (30-100 ppm), and CO exercised rats. Myocardial sensibility to IR was evaluated with a regional ischemia performed on a Langendorff model of isolated heart. Moreover, the cardiomyocytes function and calcium handling were evaluated at basal conditions, following a protocol of cellular anoxia and reoxygenation. The results of this study confirm that chronic exposure to CO is responsible for cardiac phenotypic changes, which are characterized in this work by an imbalance in the cardiomyocytes oxidative status, an impairment of calcium handling and iNOS expression. These phenotypic changes were associated in this work with higher heart vulnerability to IR. Another major result of this study is that regular bouts of endurance training conducted prior to CO exposure prevented the pathological cardiac remodeling, consequently leading to higher heart vulnerability due to IRAVIGNON-Bib. numérique (840079901) / SudocSudocFranceF