Comparison of ANP and BNP Granular Density in Atria of Rats After Physiological and Pathological Hypertrophy.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones located in atria granules. Both peptides respond to cardiac pressure and volume dynamics and accordingly serve as translation biomarkers for the clinical treatment of heart failure. Serum ANP and BNP play central secretary roles in blood pressure and cardiac output regulation and have proven utility as differential biomarkers of cardiovascular proficiency and drug-induced maladaptation, yet both peptides are impervious to exercise-induced hypertrophy. We employed immunoelectron microscopy to examine the effects of 28 days of chronic swim exercise or administration of a PPARγ agonist on atrial granules and their stored natriuretic peptides in Sprague Dawley rats. Chronic swimming and drug treatment both resulted in a 15% increase in heart weight compared with controls, with no treatment effects on perinuclear granule area in the left atria (LAs). Drug treatment resulted in larger size granules with greater BNP density in the right atria. Comparing swimming and PPARγ agonist treatment effects on ANP:BNP granule density ratios between atrial chambers revealed a shift toward a greater proportion of ANP than BNP in LAs of swim-trained rats. These data suggest a distinction in the population of ANP and BNP after chronic swim or PPARγ that makes it a novel metric for the differentiation of pathological and physiological hypertrophy.

Postmenopausal effects of resistance training on muscle damage and mitochondria.

The purpose of this study was to measure the effects of a 12-month progressive resistance training intervention on muscle morphology and strength gains in postmenopausal women. Skeletal muscle biopsies were obtained from the vastus lateralis of 5 independent community-dwelling women (mean age: 75.6 ± 4.28 years; mean height: 163 ± 5.34 cm; mean weight: 72 ± 17.5 kg) before 6 months and 12 months after progressive resistance training. Muscle strength (1 repetition maximum) was measured at the same time points. After 6 months of training, morphological analysis revealed evidence of increased proteolysis and tissue repair, and rudimentary fiber development. The percent of Z-bands with mild Z-band disruption increased from 43.9% at baseline to 66.7% after 6 months of training (p < 0.01). Mitochondrial volume also increased (percent of mitochondria = 0.86% at baseline, 1.19% at 6 months, and 1.04% at 12 months, p < 0.05), and there was a shift to larger sized mitochondria. The training did not result in statistically significant increases in muscle leg strength (p < 0.18). It appears that mild Z-band disruption acts as a precursor for increased protein synthesis and stimulates an increase in mitochondrial mass. Therefore, although a progressive resistance training program in this population did not increase muscle strength, it did demonstrate clinical applications that lend support to the importance of resistance training in older adults.

Mechanical function, glycolysis, and ultrastructure of perfused working mouse hearts following thoracic aortic constriction.

BACKGROUND: Glycolytic flux in the mouse heart during the progression of left ventricular hypertrophy (LVH) and mechanical dysfunction has not been described. METHODS: The main objectives of this study were to characterize the effects of thoracic aortic banding, of 3- and 6-week duration, on: (1) left ventricular (LV) systolic and diastolic function of perfused working hearts quantified by analysis of pressure-volume loops; (2) glycolytic flux in working hearts expressed as the rate of conversion of (3)H-glucose to (3)H(2)O, and (3) ultrastructure of LV biopsies assessed by quantitative and qualitative analysis of light and electron micrographs. RESULTS: Results revealed that (1) indexes of systolic function, including LV end-systolic pressure, cardiac output, and rate of LV pressure development and decline, were depressed to similar degrees at 3 and 6 weeks post-banding; (2) diastolic dysfunction, represented by elevated LV end-diastolic pressure and volume, was more severe at 6 than at 3 weeks, consistent with a transition to failure; (3) a progressive decline in glycolytic flux that was roughly half the control rate by 6 weeks post-banding; and (4) structural derangements, manifested by increases in interstitial collagen content and myocyte Z-band disruption, that were more marked at 3 weeks than at 6 weeks. CONCLUSION: The results are consistent with the view that myocyte damage, fibrosis, and suppressed glycolytic flux represent maladaptive structural and metabolic remodeling that contribute to the development of failure in high pressure load-induced LVH in the mouse.

Immunogold labeling of insulin growth factor-I receptors in elderly human skeletal muscle.

Age-associated muscle wasting, or sarcopenia, can be delayed or reversed with interventions, including exercise and pharmaceutical agents. Mapping morphometric changes in the skeletal muscle insulin growth factor 1 receptor can provide valuable information regarding mechanisms controlling muscle protein metabolism. Immunocolloidal gold labeling is a powerful immunocytochemistry procedure for detecting antigens at the ultrastructural level, providing plausible biological markers of cell and tissue adaptations to stimuli. The intent here was to employ immunogold labeling to identify, localize, and quantify the insulin growth factor receptor-I (IGF-IR) in elderly human skeletal muscle. Needle biopsy specimens of the leg vastus lateralis muscle were fixed with 1% glutaraldehyde and 4% paraformaldehyde, dehydrated, and embedded in LR white resin. Pilot experiments were carried out to establish optimal dilutions of primary and secondary antibodies and to employ controls to establish staining specificity. The 6 nm gold particles were first evident when viewed at transmission electron microscopy (TEM) magnifications at 54,000x and clearest at 71,000x. Consistencies were noted in the staining patterns, with the majority of particles lying in proximity to the myofilaments. Gold particles were also found randomly along the outer membrane of the sarcolemma and the mitochondrial membranes. National Institutes of Health (NIH) Image 1.55 version software was used to measure receptor density (NIH, Bethesda, Md., USA). It appears that immunogold labeling of postembedded tissue samples is a sensitive method for detecting IGF-I receptors at the ultrastructural level.

Exercise training effects on skeletal muscle plasticity and IGF-1 receptors in frail elders.

Age-related sarcopenia inhibits mobility, increasing the risk for developing many diseases, including diabetes, arthritis, osteoporosis, and heart disease. Tissue plasticity, or the ability to regenerate following stress, has been a subject of question in aging humans. We assessed the impact of 10-weeks of resistance training on markers of skeletal muscle plasticity and insulin growth factor-1 (IGF-1) receptor density in a sub sample of subjects who, in an earlier study, demonstrated enhanced immunohistochemical labeling of IGF following resistance training. Muscle biopsies from the vastus lateralis of five elderly men and women were taken prior to and following 10 weeks of resistance training (N = 3) or a control period (N = 2). Immunogold labeling and quantitative electron microscopy techniques were used to analyze markers of IGF-1 receptor density and tissue plasticity. The experimental subjects showed a 161 ± 93.7% increase in Z band damage following resistance training. Myofibrillar central nuclei increased 296 ± 120% (P = 0. 029) in the experimental subjects. Changes in the percent of damaged Z bands were associated with alterations in the presence of central nuclei (r = 0.668; P = 0.0347). Post hoc analysis revealed that the relative pre/post percent changes in myofibrillar Z band damage and central nuclei were not statistically different between the control and exercise groups. Exercise training increased myofibrillar IGF-1 receptor densities in the exercise subjects (P = 0.008), with a non-significant increase in the control group. Labeling patterns suggested enhanced receptor density around the Z bands, sarcolemma, and mitochondrial and nuclear membranes. Findings from this study suggest that the age-related downregulation of the skeletal muscle IGF-1 system may be reversed to some extent with progressive resistance training. Furthermore, skeletal muscle tissue plasticity in the frail elderly is maintained at least to some extent as exemplified by the enhancement of IGF-1 receptor density and markers of tissue regeneration.

Exercise training alters skeletal muscle mitochondrial morphometry in heart failure patients.

BACKGROUND: Previous research has demonstrated that exercise intolerance in heart failure patients is associated with significant alterations in skeletal muscle ultrastructure and oxidative metabolism that may be more consequential than cardiac output. DESIGN: To examine the effect of exercise training on skeletal muscle mitochondrial size in chronic heart failure patients. METHODS: Six heart failure patients participated in 16-weeks of supervised upper and lower extremity exercise training. At the conclusion of training, percutaneous needle biopsies of the vastus lateralis were taken and electron microscopy was used to assess mitochondrial sizes. RESULTS: The exercise programme resulted in a significant increase in peak maximal oxygen consumption ( P< 0.05) and anaerobic threshold (P < 0.04). Knee extension muscle force increased following training ( P< 0.02). After exercise training, the average size of the mitochondria increased by 23.4% (0.036 to 0.046 mu(2), P< 0.015) and the average shape was unaltered. CONCLUSION: Exercise training with heart failure patients alters skeletal muscle morphology by increasing mitochondrial size, with no change in shape. This may enhance oxidative metabolism resulting in an increased exercise tolerance.