RESUMEN
We evaluated the influence of aerobic exercise on cardiac remodelling during the transition from compensated left ventricular (LV) hypertrophy to clinical heart failure in aortic stenosis (AS) rats. Eighteen weeks after AS induction, rats were assigned into sedentary (AS) and exercised (AS-Ex) groups. Results were compared to Sham rats. Exercise was performed on treadmill for 8 weeks. Exercise improved functional capacity. Echocardiogram showed no differences between AS-Ex and AS groups. After exercise, fractional shortening and ejection fraction were lower in AS-Ex than Sham. Myocyte diameter and interstitial collagen fraction were higher in AS and AS-Ex than Sham; however, myocyte diameter was higher in AS-Ex than AS. Myocardial oxidative stress, evaluated by lipid hydroperoxide concentration, was higher in AS than Sham and was normalized by exercise. Gene expression of the NADPH oxidase subunits NOX2 and NOX4, which participate in ROS generation, did not differ between groups. Activity of the antioxidant enzyme superoxide dismutase was lower in AS and AS-Ex than Sham and glutathione peroxidase was lower in AS-Ex than Sham. Total and reduced myocardial glutathione, which is involved in cellular defence against oxidative stress, was lower in AS than Sham and total glutathione was higher in AS-Ex than AS. The MAPK JNK was higher in AS-Ex than Sham and AS groups. Phosphorylated P38 was lower in AS-Ex than AS. Despite improving functional capacity, aerobic exercise does not change LV function in AS rats. Exercise restores myocardial glutathione, reduces oxidative stress, impairs JNK signalling and further induces myocyte hypertrophy.
Asunto(s)
Estenosis de la Válvula Aórtica/fisiopatología , Glutatión Peroxidasa/metabolismo , Insuficiencia Cardíaca/patología , Hipertrofia Ventricular Izquierda/patología , Condicionamiento Físico Animal , Función Ventricular Izquierda/fisiología , Animales , Antioxidantes/metabolismo , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/rehabilitación , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/rehabilitación , Masculino , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
BACKGROUND: The allele threonine (T) of the angiotensinogen has been associated with ventricular hypertrophy in hypertensive patients and soccer players. However, the long-term effect of physical exercise in healthy athletes carrying the T allele remains unknown. We investigated the influence of methionine (M) or T allele of the angiotensinogen and D or I allele of the angiotensin-converting enzyme on left-ventricular mass index (LVMI) and maximal aerobic capacity in young healthy individuals after long-term physical exercise training. DESIGN: Prospective clinical trial. METHODS: Eighty-three policemen aged between 20 and 35 years (mean+/-SD 26+/-4.5 years) were genotyped for the M235T gene angiotensinogen polymorphism (TT, n = 25; MM/MT, n = 58) and angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism (II, n = 18; DD/DI, n = 65). Left-ventricular morphology was evaluated by echocardiography and maximal aerobic capacity (VO2peak) by cardiopulmonary exercise test before and after 17 weeks of exercise training (50-80% VO2peak). RESULTS: Baseline VO2peak and LVMI were similar between TT and MM/MT groups, and II and DD/DI groups. Exercise training increased significantly and similarly VO2peak in homozygous TT and MM/MT individuals, and homozygous II and DD/DI individuals. In addition, exercise training increased significantly LVMI in TT and MM/MT individuals (76.5+/-3 vs. 86.7+/-4, P = 0.00001 and 76.2+/-2 vs. 81.4+/-2, P = 0.00001, respectively), and II and DD/DI individuals (77.7+/-4 vs. 81.5+/-4, P = 0.0001 and 76+/-2 vs. 83.5+/-2, P = 0.0001, respectively). However, LVMI in TT individuals was significantly greater than in MM/MT individuals (P = 0.04). LVMI was not different between II and DD/DI individuals. CONCLUSION: Left-ventricular hypertrophy caused by exercise training is exacerbated in homozygous TT individuals with angiotensinogen polymorphism.
Asunto(s)
Angiotensinógeno/genética , Terapia por Ejercicio/métodos , Hipertrofia Ventricular Izquierda/genética , Hipertrofia Ventricular Izquierda/rehabilitación , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Adulto , Alelos , Análisis de Varianza , Brasil , Prueba de Esfuerzo , Genotipo , Humanos , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Consumo de Oxígeno/fisiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
El sistema renina-angiotensina tisular y su producto final, al angiotensina II, es uno de los reguladores más importantes de la estructura y función del corazón y los vasos sanguíneos, por lo que una activación crónica de este sistema en estos tejidos puede producir cambios deletéreos a largo plazo. En el presente artículo se exponen los principales mecanismos por los cuales el sistema renina-angiotensina tisular ejerce su función y se resalta la importancia de su inhibición para la prevención de situaciones perjudiciales como son la hipertrofia cardíaca y la cicatrización posterior a eventos isquémicos