Effects of altered thyroid status on beta-adrenergic actions on skeletal muscle glycogen metabolism

The effects of hypothyroidism on glycogen metabolism in rat skeletal muscle were studied using the perfused rat hindlimb preparation. Three weeks after propylthiouracil treatment, serum thyroxine was undetectable and muscle glycogen and Glc-6-P were decreased. Basal and epinephrine-stimulated phosphorylase a and phosphorylase b kinase activities were also significantly reduced, as were epinephrine-stimulated cAMP accumulation and cAMP-dependent protein kinase activity. Conversely, basal and epinephrine-stimulated glycogen synthase I activities were significantly higher while the Ka of the enzyme for Glc-6-P was lower in hypothyroid animals. Propylthiouracil-treated rats also had increased phosphoprotein phosphatase activities towards phosphorylase and glycogen synthase and decreased activity of phosphatase inhibitor 1. beta-Adrenergic receptor binding and basal and epinephrine-stimulated adenylate cyclase activities were reduced in muscle particulate fractions from hypothyroid rats. Administration of triiodothyronine to rats for 3 days after 3 weeks of propylthiouracil treatment restored the altered metabolic parameters to normal. It is proposed that the decreased beta-adrenergic responsiveness of the enzymes of glycogen metabolism in hypothyroid rat skeletal muscle is due to increased activity of phosphoprotein phosphatases and to reduced beta-adrenergic receptors and adenylate cyclase activity.     

Postradiation changes in the thyroid gland and skeletal muscle after exposure to iodine-131

The functional status of rat skeletal muscles was studied at dormancy and during the intensive muscular work under conditions of repeated administration of iodine 131 in doses causing reversible and irreversible damages to thyroid gland (the absorbed doses were from 0.27 to 266 Gy). The biochemical changes in muscles were transient; they correlated with the thyroid gland status and lifetime of animals and were displayed during the first 15 days and 2-12 months after the start of the isotope injection.     

Temperature-dependent skeletal muscle dysfunction in rats with congestive heart failure.

Abnormalities in the excitation-contraction coupling of slow-twitch muscle seem to explain the slowing and increased fatigue observed in congestive heart failure (CHF). However, it is not known which elements of the excitation-contraction coupling might be affected. We hypothesize that the temperature sensitivity of contractile properties of the soleus muscle might be altered in CHF possibly because of alterations of the temperature sensitivity of intracellular Ca(2+) handling. We electrically stimulated the in situ soleus muscle of anesthetised rats that had 6-wk postinfarction CHF using 1 and 50 Hz and using a fatigue protocol (5-Hz stimulation for 30 min) at 35, 37, and 40 degrees C. Ca(2+) uptake and release were measured in sarcoplasmic reticulum vesicles at various temperatures. Contraction and relaxation rates of the soleus muscle were slower in CHF than in sham at 35 degrees C, but the difference was almost absent at 40 degrees C. The fatigue protocol revealed that force development was more temperature sensitive in CHF, whereas contraction and relaxation rates were less temperature sensitive in CHF than in sham. The Ca(2+) uptake and release rates did not correlate to the difference between CHF and sham regarding contractile properties or temperature sensitivity. In conclusion, the discrepant results regarding altered temperature sensitivity of contraction and relaxation rates in the soleus muscle of CHF rats compared with Ca(2+) release and uptake rates in vesicles indicate that the molecular cause of slow-twitch muscle dysfunction in CHF is not linked to the intracellular Ca(2+) cycling.     

Selenium and rubidium changes in subjects with pathologically altered thyroid

Concentrations of selenium and rubidium in groups of subjects with hyperthyroidism, carcinomas, or adenomas and in controls were determined by neutron activation analysis with coirradiated inorganic standards and IAEA reference material. Se was decreased in all pathological groups with the greatest modification in thyroids with carcinomas. Rb was elevated in all pathological groups with the greatest increase in carcinomas as well. According to the literature, Se has a protective effect on carcinogenity as well as on biochemical pathways in thyroid cells. There are no data in the literature on the effects of Rb in those cells. On the grounds of the present results, it seems possible to use the trapping of Rb for diagnostic purposes in cases of pathologically altered thyroids.     

Exercise training prevents skeletal muscle afferent sensitization in rats with chronic heart failure

An exaggerated exercise pressor reflex (EPR) contributes to exercise intolerance and excessive sympathoexcitation in the chronic heart failure (CHF) state, which is prevented by exercise training (ExT) at an early stage in the development of CHF. We hypothesized that ExT has a beneficial effect on the exaggerated EPR by improving the dysfunction of muscle afferents in CHF. We recorded the discharge of mechanically sensitive (group III) and metabolically sensitive (group IV) afferents in response to static contraction, passive stretch, and hindlimb intra-arterial injection of capsaicin in sham+sedentary (Sed), sham+ExT, CHF+Sed, and CHF+ExT rats. Compared with sham+Sed rats, CHF+Sed rats exhibited greater responses of group III afferents to contraction and stretch, whereas the responses of group IV afferents to contraction and capsaicin were blunted. ExT prevented the sensitization of group III responses to contraction or stretch and partially prevented the blunted group IV responses to contraction or capsaicin in CHF rats. Furthermore, we investigated whether purinergic 2X (P2X) and transient receptor potential vanilloid 1 (TRPV1) receptors mediate the altered sensitivity of muscle afferents by ExT in CHF. We found that the upregulated P2X and downregulated TRPV1 receptors in L4/5 dorsal root ganglia of CHF rats were normalized by ExT. Hindlimb intra-arterial infusion of a P2X antagonist attenuated the group III response to contraction or stretch in CHF rats to a greater extent than in sham rats, which was normalized by ExT. These findings suggest that ExT improves the abnormal sensitization of muscle afferents in CHF at least, in part, via restoring the dysfunction of P2X and TRPV1 receptors.     

Training-induced changes in skeletal muscle Na+-K+ pump number and isoform expression in rats with chronic heart failure.

The mechanisms responsible for the decrements in exercise performance in chronic heart failure (CHF) remain poorly understood, but it has been suggested that sarcolemmal alterations could contribute to the early onset of muscular fatigue. Previously, our laboratory demonstrated that the maximal number of ouabain binding sites (B(max)) is reduced in the skeletal muscle of rats with CHF (Musch TI, Wolfram S, Hageman KS, and Pickar JG. J Appl Physiol 92: 2326-2334, 2002). These reductions may coincide with changes in the Na(+)-K(+)-ATPase isoform (alpha and beta) expression. In the present study, we tested the hypothesis that reductions in B(max) would coincide with alterations in the alpha- and beta-subunit expression of the sarcolemmal Na(+)-K(+)-ATPase of rats with CHF. Moreover, we tested the hypothesis that exercise training would increase B(max) along with producing significant changes in alpha- and beta-subunit expression. Rats underwent a sham operation (sham; n = 10) or a surgically induced myocardial infarction followed by random assignment to either a control (MI; n = 16) or exercise training group (MI-T; n = 16). The MI-T rats performed exercise training (ET) for 6-8 wk. Hemodynamic indexes demonstrated that MI and MI-T rats suffered from severe left ventricular dysfunction and congestive CHF. Maximal oxygen uptake (Vo(2 max)) and endurance capacity (run time to fatigue) were reduced in MI rats compared with sham. B(max) in the soleus and plantaris muscles and the expression of the alpha(2)-isoform of the Na(+)-K(+)-ATPase in the red portion of the gastrocnemius (gastrocnemius(red)) muscle were reduced in MI rats. After ET, Vo(2 max) and run time to fatigue were increased in the MI-T group of rats. This coincided with increases in soleus and plantaris B(max) and the expression of the alpha(2)-isoform in the gastrocnemius(red) muscle. In addition, the expression of the beta(2)-isoform of the gastrocnemius(red) muscle was increased in the MI-T rats compared with their sedentary counterparts. This study demonstrates that CHF-induced alterations in skeletal muscle Na(+)-K(+)-ATPase, including B(max) and isoform expression, can be partially reversed by ET.     

Genetic parameters of body weight, muscle weight and skeletal characteristics in Japanese quail

Heritability, phenotypic and genetic correlations of body weight, muscle weight and skeletal characteristics of Japanese quail males at 8 weeks of age were investigated to obtain basal information on breeding and on genetic monitoring by morphometrical methods. For this study, 221 male progenies were used. Measurements were taken on body weight, muscle weight and four kind of skeletal characteristics (skeletal weight, skeletal length, skeletal width and skeletal height). Heritability estimates were 0.67 for body weight, 0.36 to 0.56 for muscle weight, 0.79 to 0.94 for skeletal weight, 0.35 to 0.77 for skeletal length, 0.17 to 0.32 for skeletal width and 0.41 to 0.84 for skeletal height, respectively. The phenotypic and genetic correlations were found to be highly positive between body weight, muscle weight and skeletal length. A high degree of genetic correlation was observed between femur length, ossa cruris length and ossa metatarsalia length. These results suggest that the body weight, muscle weight and skeletal characteristics can be improved by breeding and that these genetically determined skeletal characteristics might serve for strain identification and genetic monitoring in Japanese quail.     

Isolated hearts treated with skeletal muscle homogenates exhibit altered function

Skeletal muscle fiber damage and necrosis can result in the release of intracellular molecules into the extracellular environment. These molecules, termed damage-associated molecular patterns (DAMPs), can act as signals capable of initiating immune and/or inflammatory responses through interactions with pattern recognition receptors. To investigate whether skeletal muscle DAMPs interact with the heart and alter cardiac function, isolated rat hearts were perfused for 75 min with buffer containing 1 μg/ml of either soleus (slow), white gastrocnemius (WG, fast), or heat-stressed white gastrocnemius (HSWG) skeletal muscle homogenates. Left ventricular developed pressure (LVDP) and rates of pressure increase/decrease (±dP/dt) were measured using the Langendorff technique. Compared to controls, no changes in LVDP or +dP/dt were observed over the 75-min perfusion when homogenates from the WG muscles were added. In contrast, at 30 min and thereafter, a decreased LVDP and +dP/dt was observed in the hearts treated with soleus muscle homogenates. The hearts treated with HSWG homogenates also showed a decrease in LVDP from 45 min until the end of perfusion. These results suggest that molecules present in slow muscle and heat-stressed muscle are capable of altering cardiac function. Thus, muscle fiber type and/or heat shock protein content of skeletal muscles may be factors that influence cardiac function following skeletal muscle damage.     

Glycogen and glycogen enzymes in the liver and striated muscle of rats under altered thyroid states

Changes induced in liver and striated muscle glycogen and glycogen enzymes (glycogen synthetase, glycogen phosphorylase and alpha-amylase) by hypothyroidism and hyperthyroidism in rats have been determined. There were no changes in liver glycogen synthetase, phosphorylase and amylase activities in the hypothyroid group. Hyperthyroid rats showed lower liver glycogen synthetase, phosphorylase a and amylase activities. In muscle, hypothyroid rats had lower phosphorylase activity. In the hyperthyroid group glycogen synthetase was increased.--The results presented do not completely agree with the glycogen levels found in both tissues studied, and they are obviously more related to other factors such as glucose availability. It can be concluded that under the conditions studied, the glycogen enzyme levels could not alone explain the variations of glycogen levels.     

Body height,weight, and skeletal maturation in Hottentot (Khoikhoi) children

Growth of body height and weight and skeletal maturation are discussed, based on 49 male and 61 female Hottentot children aged 3 to 17 years from Warmbad, Namibia (South West Africa) and 124 boys and 113 girls aged 1 to 21 years of related populations, the Rehoboth Basters of Namibia and Cape Coloreds from Cape Town, South Africa. The related populations are taller and heavier than the Hottentots, and have almost the same body height as American blacks and whites at least after the age of 18 years. In the Hottentots and Rehoboth Basters, the mean TW2 skeletal age is always less than the British standard by one or two years in both sexes. In general, the Rehoboth Basters have a skeletal age that is intermediate between Hottentot and British children. In both Hottentots and Rehoboth Basters, the increase in body height shows a linear relation to the skeletal age, and the regression curves are almost parallel in both sexes. The differences in body height and weight between the Hottentots and Rehoboth Basters become greater after the skeletal ages of 15 years for boys and 13 years for girls.     

Increased DNA fragmentation and altered apoptotic protein levels in skeletal muscle of spontaneously hypertensive rats.

Apoptosis is a highly conserved process that plays an important role in controlling tissue development, homeostasis, and architecture. Dysregulation of apoptosis is a hallmark of numerous human pathologies including hypertension. In the present work we studied the effect of hypertension on apoptosis and the expression of several apoptotic signaling and/or regulatory proteins in four functionally and metabolically distinct muscles. Specifically, we examined these markers in soleus, red gastrocnemius, white gastrocnemius, and left ventricle (LV) of 20-wk-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Compared with WKY rats SHR had a significantly greater heart weight, LV weight, and mean arterial pressure. In general, SHR skeletal muscle had increased Bax protein, procaspase-3 protein, caspase-3 activity, cleaved poly(ADP-ribose) polymerase protein, and DNA fragmentation as well as decreased Bcl-2 protein and a lower Bcl-2-to-Bax ratio. Subcellular distribution studies demonstrated increased levels of apoptosis-inducing factor protein in cytosolic or nuclear extracts as well as elevated nuclear Bax protein in SHR skeletal muscle. Moreover, heat shock protein 70 in red gastrocnemius and soleus was significantly correlated to several apoptotic factors. With the exception of lower heat shock protein 90 levels in SHR no additional differences in any apoptotic markers were observed in LV between groups. Collectively, this report provides the first evidence that apoptotic signaling is altered in skeletal muscle of hypertensive animals, an effect that may be mediated by both caspase-dependent and -independent mechanisms. This proapoptotic state may provide some understanding for the morphological and functional abnormalities observed in skeletal muscle of hypertensive animals.     

Attenuated fatigue in slow twitch skeletal muscle during isotonic exercise in rats with chronic heart failure

During isometric contractions, slow twitch soleus muscles (SOL) from rats with chronic heart failure (chf) are more fatigable than those of sham animals. However, a muscle normally shortens during activity and fatigue development is highly task dependent. Therefore, we examined the development of skeletal muscle fatigue during shortening (isotonic) contractions in chf and sham-operated rats. Six weeks following coronary artery ligation, infarcted animals were classified as failing (chf) if left ventricle end diastolic pressure was >15 mmHg. During isoflurane anaesthesia, SOL with intact blood supply was stimulated (1s on 1s off) at 30 Hz for 15 min and allowed to shorten isotonically against a constant afterload. Muscle temperature was maintained at 37°C. In resting muscle, maximum isometric force (F(max)) and the concentrations of ATP and CrP were not different in the two groups. During stimulation, F(max) and the concentrations declined in parallel sham and chf. Fatigue, which was evident as reduced shortening during stimulation, was also not different in the two groups. The isometric force decline was fitted to a bi-exponential decay equation. Both time constants increased transiently and returned to initial values after approximately 200 s of the fatigue protocol. This resulted in a transient rise in baseline tension between stimulations, although this effect which was less prominent in chf than sham. Myosin light chain 2s phosphorylation declined in both groups after 100 s of isotonic contractions, and remained at this level throughout 15 min of stimulation. In spite of higher energy demand during isotonic than isometric contractions, both shortening capacity and rate of isometric force decline were as well or better preserved in fatigued SOL from chf rats than in sham. This observation is in striking contrast to previous reports which have employed isometric contractions to induce fatigue.     

Histological demonstration of capillaries, interstitial space and muscle fibers in heart and skeletal muscle with fluorescent dyes

A method is described which allows a clear demonstration of capillaries and muscle fibers in the heart and skeletal muscle of experimental animals. The fluorescent dyes fluorescein isothiocyanate (FITC) and lissamine rhodamine B 200 (RB 200) were conjugated with a protein of high (gamma-globulin) and low (myoglobin) molecular weight, respectively, and were intravitally injected into the vascular system of rats. FITC globulin distributes itself in the intravasal space and RB 200 myoglobin in the extracellular. In histological sections the capillary lumina and the borderlines of the muscular fibers can be clearly identified and quantitatively evaluated because of the selective fluorescence in the respective structures.     

Isolation of camel brain actin--comparison of its biochemical properties with those of camel skeletal muscle, heart muscle and rabbit skeletal muscle actins

1. Actins were purified from camel brain, skeletal muscle and heart muscle and their properties were compared. 2. Individual actins were homogeneous and comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). 3. Isoelectric focusing analysis of camel skeletal muscle and heart muscle actin showed a single polypeptide of the alpha-species, while camel brain actin showed two polypeptides of the beta- and gamma-species typical of non-muscle actin. 4. Actins from camel skeletal muscle and heart muscle showed a greater degree of similarity to each other and to rabbit skeletal muscle actin and showed some differences from camel brain actin, as confirmed by amino acid analysis and one-dimensional peptide mapping.