ANG II is required for optimal overload-induced skeletal muscle hypertrophy.
ABSTRACT ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.
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ABSTRACT: Physical performance in response to exercise appears to be influenced by the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) genotype in young adults, but whether this relationship could help explain variation in older individuals' response to exercise has not been well studied. To determine whether the ACE genotype interacts with significant physical activity to affect the incidence of mobility limitation in well-functioning older adults. The Health Aging and Body Composition (Health ABC) Cohort Study, conducted in the metropolitan areas of Memphis, Tenn, and Pittsburgh, Pa. A total of 3075 well-functioning community-dwelling adults aged 70 through 79 years were enrolled from 1997 to 1998 and had a mean of 4.1 years of follow-up. Incident mobility limitation defined as the report of difficulty walking a quarter of a mile (0.4 km) or walking up 10 steps on 2 consecutive semiannual interviews (n = 1204). Physically active participants (those reporting expending > or =1000 kcal/wk in exercise, walking, and stair climbing) were less likely to develop mobility limitation regardless of genotype. However, activity level interacted significantly with the ACE genotype (P = .002). In the inactive group, the ACE genotype was not associated with limitation (P = .46). In the active group, those with the II genotype were more likely to develop mobility limitation after adjusting for potential confounders compared with those with ID/DD genotypes (adjusted rate ratio, 1.45, 95% confidence interval, 1.08-1.94). The gene association was especially strong among participants reporting weightlifting. Exploration of possible physiological correlates revealed that among active participants, those with the II genotype had higher percentage of body fat (P = .02) and more intermuscular thigh fat (P = .02) but had similar quadriceps strength as those with ID/DD. Among older individuals who exercised, those with the ACE DD or ID genotypes were less likely to develop mobility limitation than those with the II genotype. Regardless of genotype, individuals who exercised were less likely to develop mobility limitation than those who did not exercise.JAMA The Journal of the American Medical Association 08/2005; 294(6):691-8. · 30.03 Impact Factor
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ABSTRACT: The role of angiotensin II (Ang II) in skeletal muscle is poorly understood. We report that pharmacological inhibition of Ang II signaling or ablation of the AT1a receptor significantly impaired skeletal muscle growth following myotrauma, in vivo, likely due to impaired satellite cell activation and chemotaxis. In vitro experiments demonstrated that Ang II treatment activated quiescent myoblasts as evidenced by the upregulation of myogenic regulatory factors, increased number of β-gal+, Myf5-LacZ myoblasts and the acquisition of cellular motility. Furthermore, exogenous treatment with Ang II significantly increased the chemotactic capacity of C2C12 and primary cells while AT1a(-/-) myoblasts demonstrated a severe impairment in basal migration and were not responsive to Ang II treatment. Additionally, Ang II interacted with myoblasts in a paracrine-mediated fashion as 4 h of cyclic mechanical stimulation resulted in Ang II-induced migration of cocultured myoblasts. Ang II-induced chemotaxis appeared to be regulated by multiple mechanisms including reorganization of the actin cytoskeleton and augmentation of MMP2 activity. Collectively, these results highlight a novel role for Ang II and ACE inhibitors in the regulation of skeletal muscle growth and satellite cell function.PLoS ONE 01/2010; 5(12):e15212. · 4.09 Impact Factor
Article: The angiotensin converting enzyme gene insertion / deletion polymorphism in Lithuanian professional athletes[show abstract] [hide abstract]
ABSTRACT: Background. Human ACE gene was one of the first genes to be associated with human physical performance. Previous studies have indicated that Alu insertion and deletion polymorphism (I / D polymorphism) in the ACE gene may be associated with elite athlete status. Materials and methods. ACE I/D polymorphism was investigated by PCR and gel electrophoresis in 561 Lithuanian professional athletes and in 174 samples from general population of Lithuania. Results. Genotypes for athletes were identified as I / I 24.8%, I / D 47.2% and D / D 28% (÷2 = 1.65, p = 0.19) and in the population samples as I / I 24.1%, I / D 38.5% and 37.4% (÷2 = 8.13, p = 0.004). In comparison with the general Lithuanian population, the tested athletes had a lower frequency of ACE D allele. The results of this research contradict the results reported on other populations: the D / D genotype was found to be less frequent in all Lithuanian athlete groups than in general population, whereas, according to other researchers, the D / D genotype is more frequent in athletes. Athletes assigned to the endurance sports group had a lower frequency of the D / D genotype than athletes in the speed / strength group, whereas other researchers have reported a higher frequency of D / D genotype in endurance groups. Conclusion. The ACE D / D genotype was less frequent in athletes than in the general population. Athletes of endurance sports had a higher frequency of D / D genotype than athletes assigned to the speed / strength sports group. These results do not support the results of other investigations conducted in other populations, in which the I allele of the ACE gene was found to determine superior endurance.acta medica lituanica. 12/2009; 16(1):11-16.