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Rats were trained by daily swimming or running exercises with and without daily propranolol injections. Both training methods resulted in cardiac enlargement, but only swimming exercise caused hypertrophy of the brown adipose tissue. These changes were antagonized by beta blockade. The size of the adrenals reflected the stress of the treatments, but other known stress parameters, such as the size of the thymus or sexual organs dit not. Only swimming training without beta blockade sensitized the rats to the calorigenic action of noradrenaline. The cooling rate of the rats in water, when taking into account the insulative capacity of the body, was decreased in swimming-trained as well as in propranolol-treated rats but increased in running-trained rats. The latter two changes may be due to circulatory alterations, while the delayed body cooling in swimming-trained rats probably results from increased heat production capacity. Training-induced resting bradycardia and enhanced tachycardic response to isoprenaline were observable only in the animal groups trained without beta blockade. The pressor response to noradrenaline tended to be higher in the trained groups and the propranolol-treated group than in the controls and was smaller in the animal groups trained under the influence of beta blockade. On the other hand, the hypotonic response to isoprenaline was smaller in the propranolol-treated and running-trained animals. The results emphasize the importance of the sympathetic nervous system in the adaptation of an organism to physical training.

The metabolic effects on rat cardiac and skeletal muscle of a strenous program of swimming, of cold acclimation and of isoprenaline treatment (0.3 mg/kg daily for 5 five-day weeks) were compared. Exercised and cold-exposed rats gained less body weight than did controls or isoprenaline-treated rats. In all treated groups the heart and the intercapular brown adipose tissue hypertrophied. The size of the adrenals increased only in isoprenaline-treated animals. Cold-acclimation and physical training increased and isoprenaline treatment reduced or did not affect the activities of succinate dehydrogenase, malate dehydrogenase and citrate synthase of cardiac muscle. In the skeletal muscle all treatments resulted in increased activities of these enzymes. Of the anaerobic enzymes analysed, only the activity of hexokinase increased in response to the treatements used. This increase was the same in cardiac as in skeletal muscle, but it was significantly greater with isoprenaline-treatment than with training or with cold-acclimation. The activities of lactate dehydrogenase and phosphofructokinase did not differ significantly. All treatments improved cold resistance, but only swimming exercise and cold acclimation significantly increased tolerance to exercise. It is concluded that prolonged stimulation of adrenergic beta-receptors by catecholamines is responsible for the metabolic changes observed.

Decreased chronotropic and inotropic sensitivity of isolated atria to phenylephrine but not to isoprenaline was found in rats following repeated physical training by swimming or repeated ACTH-injections. These changes were induced within a week of subjection of animals to these treatments. It is concluded, that these effects are mediated by increased adrenergic activity which results in this subsensitivity of alpha-receptors.

Rats were treated by daily swimming or running exercises for 7 weeks. One group of rats was also trained under the influence of propranolol, while another group received daily propranolol injections only. The rat groups trained without beta blockade maintained a higher tail skin temperature when exposed to 5 degrees C after the 7-week training period. This phenomenon was not observable in the animals having received their training under the influence of beta-blockade. Both rat groups trained without beta-blockade showed increased vasodilatatory response to isoprenaline, as judged from a higher elevation of the tail skin temperature in response to the drug. This response was absent in the animal group having performed its training periods under the influence of propranolol. After the injection of phenylephrine the trained rats had a higher tail skin temperature than did the controls or propranolol-treated rats. The present results suggest an elevated sensitivity of beta 2-adrenoceptors and/or decreased sensitivity of alpha-adrenoceptors in trained rats. It is suggested that for the development of these changes repeated activation of the sympathetic nervous system by exercise periods is needed. That is why they are preventable if the training is performed under the influence of beta-blockade.

Repeated daily exposures of rats to a hot ambient temperature (40-41 degrees C) for 20 days induced activation of the oxidative enzymes in the thigh muscle and of lactate dehydrogenase in the myocardium. Heat-stressed rats also showed increased tolerance to cold. These changes, it is suggested, are caused by the increased sympathetic activity bouts associated with the heat stresses. The interscapular brown adipose tissue, however, showed adaptive changes similar to those induced by warm acclimation. The activity of oxidative enzymes was decreased and the fat droplets became large and unilocular.

Repeated injections of rat with 1-thyroxine (50 microgram/kg daily for 5 five-day weeks) retarded the weight gain of the animals and increased the absolute and relative size of the heart, adrenals and interscapular brown adipose tissue. In the myocardium and thigh muscle, thyroxine treatment resulted in elevated activity of oxidative enzymes, succinate dehydrogenase, malate dehydrogenase and citrate synthase, while the activities of glycolytic enzymes remained unchanged. Glycogen content of the heart was decreased following thyroxine regime. In the brown fat, on the other hand, thyroxine injections resulted in a reduction of the activity of oxidative enzymes. This reduction can be accounted for by the decreased protein (enzyme) content of the tissue due to deposition of fat. Furthermore, thyroxine treatment delayed the body cooling of the rats swimming in water at 25 degrees C and enhanced hyperthermic response to injected noradrenaline. All these changes, which were not observable in rats treated with daily alprenolol (20 mg/kg) injections, were as pronounced in rats injected with alprenolol together with thyroxine as in rats injected with thyroxine only. It is concluded that beta blockers do not antagonize the metabolic changes due to hyperthyroidism.

Rats were trained by daily running exercises for 7 weeks. In addition, one group of rats was trained under the influence of propranolol, while another group received daily injections of propranolol only. None of the treatments used had influence on the activities of myocardial enzymes: 3-hydroxyacyl-CoA - dehydrogenase (HADH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and citrate synthase (CS) which were assayed for estimating oxidative capacity, or lactate dehydrogenase (LDH) which was used as a measure of anaerobic capacity. Training without propranolol resulted in elevated activities of the oxidative enzymes in M. extensor digitorum and in M. soleus. The corresponding changes in the rat group trained with propranolol always were much smaller, despite an equal amount of training. Only the trend for lowered activity of LDH was observable in skeletal muscle of the rat groups trained both with and without propranolol. Long-term beta-blockade alone did not induce enzymatic changes. It is concluded that a functioning sympathetic nervous system is necessary for the adaptive responses of muscular metabolism to training. Blockade of the sympathetic influence during exercise periods also hampers the training-induced responses.

Rats were treated by daily alprenolol (10, 20 and 50 mg/kg) injections for 5 days a week for 4 weeks. At 20--21 degrees C alprenolol treatment retarded the weight gain of the animals and increased the weight of the adrenals. These changes were not seen at 29 degrees C. The reduction in size and fat content of the interscapular brovin adipose tissue in drug-treated rats was independent of experimental temperature. At 20--21 degrees C prolonged beta-blockade did not cause any changes in the enzymes of the energy metabolism. At 29 degrees C, however, alprenolol treatment antagonized the decrease in activity of oxidative enzymes (succinate dehydrogenase, malate dehydrogenase, citrate synthase) and the decrease in protein concentration of the cardiac muscle. In skeletal muscle alprenolol treatment significantly decreased the activities of oxidative enzymes and antagonized the rise in the activity of lactate dehydrogenase resulting from warm acclimation. The increased activities of oxidative enzymes in interscapular brown adipose tissue of aprenolol treated rats were coupled with an increase in protein concentration of the tissue. Although these changes were more marked at 29 degree C they were observable at 20--21 degree C, too. The difference in the drug effects at 20--21 degrees C and 29 degrees C can be accounted for by the compensatory catecholamine release at the lower temperature, due to impaired thermoregulatory capacity after alprenolol. Prolonged beta blockade decreased the exercise tolerance and cold tolerance of the rats. An increased response of the diastolic blood pressure to an alpha-adrenergic drug, noradrenaline, and a decreased response to a beta-adrenergic drug, isoprenaline, in alprenolol-treated rats indicates a shift from beta- to alpha-receptors.

Rats were given daily injections of noradrenaline (0.5 mg/kg), alprenolol (20 mg/kg), or both together for 17 to 39 days. Noradrenaline injections increased the size of the heart, interscapular brown adipose tissue (ISBAT) and, when the injections were given at a thermoneutral environment, the metabolic activity of the ISBAT. Alprenolol injections tended to reduce the size of the heart and ISBAT and, at a thermoneutral environment, metabolic activity of the skeletal muscle. Furthermore, noradrenaline treatment improved tolerance against body cooling in water at 25 degrees C and enhanced calorigenic response to injected noradrenaline. The metabolic alterations in the rats injected with both drugs together resembled more those of the animals injected with alprenolol only than those of the noradrenaline treated rats. It can be thus concluded that alprenolol, when given together with noradrenaline, antagonized noradrenaline-induced metabolic alterations in the organism. However, the increased pressor response to infused noradrenaline, which was evident in the alprenolol treated animals, was not seen in the animals treated with both drugs. By contrast, these animals, like also the noradrenaline-treated animals, showed decreased pressor response to noradrenaline. This finding suggests that prolonged beta blockade does not abolish the decreased sensitivity of alpha-adrenoreceptors following prolonged noradrenaline load. On the other hand, the hypotonic response to a beta adrenergic drug, isoprenaline, was reduced by prolonged beta blockade despite simultaneous noradrenaline injections.

Host-parasite interactions can be harmful or harmless depending on the fitness and stress levels of the organisms. Interactions between the endocrine system, the immune system and energy expenditure are critical in the maintenance of homeostasis during stressful periods in vertebrates. We examined whether lungworm loads (Rhabdias spp.) of male cane toad (Rhinella marina) sampled during the wet season from three different populations, are associated with hormone levels, immune competence, and metabolic status. We found evidence of direct and strong associations between parasite burdens and variables related to hormonal levels, metabolic status and immune competence. We also found that interrelationships among independent variables can change the strength of the association with lungworm loads. These findings suggest that high levels of corticosterone affect immune competence against parasites, both directly and by inducing changes in the metabolic status of the animals. Additionally, high testosterone levels during the reproductive season, influenced variables related to metabolic status, which will also lead to higher parasite loads. Overall, we conclude that the endocrine system and metabolic status in male cane toads are critical to the immune competence against parasites during the reproductive season. [ABSTRACT FROM AUTHOR]

Effective aerobic locomotion depends on adequate delivery of oxygen and an appropriate allocation of metabolic substrates. The use of metabolic substrates during exercise follows a predictive pattern of lipid and carbohydrate oxidation that is similar in lowland native cursorial mammals. We have found that in two highland lineages of mice (Phyllotis and Peromyscus) the fuel use pattern is shifted to a greater reliance on carbohydrates compared to their lowland conspecifics and congenerics. However, there is variation between lineages in the importance of phenotypic plasticity in the expression of this metabolic phenotype. Moreover, this metabolic phenotype is independent of running aerobic capacity and can also be independent of thermogenic capacity. For example, wild-caught mice from a highland population of deer mice (Peromyscus maniculatus) housed in warm normoxic laboratory conditions maintain higher maximum cold-induced oxygen consumption in acute hypoxia than lowland congenerics, but shivering and non-shivering thermogenesis is supported by high rates of lipid oxidation. This is reflected in the consistently higher activities of oxidative and fatty acid oxidation enzymes in the gastrocnemius of highland deer mice compared to lowlanders, which are resistant to hypoxia acclimation. While a fixed trait in muscle aerobic capacity may reflect the pervasive and unremitting low PO2 at high altitudes, muscle capacities for substrate oxidation may be more flexible to match appropriate substrate use with changing energetic demands. How shivering thermogenesis and locomotion potentially interact in the matching of muscle metabolic capacities to appropriate substrate use is unclear. Perhaps it is possible that shivering serves as "training" to ensure muscles have the capacity to support locomotion or visa-versa. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis, a known risk factor for heart disease, is typically caused by uncontrolled proliferation of fibroblasts and excessive deposition of extracellular matrix proteins in the myocardium. Cyclin-dependent kinase 1 (CDK1) is involved in the control of G2/M transit phase of the cell cycle. Here, we showed that isoproterenol (ISO)-induced cardiac fibrosis is associated with increased levels of CDK1 exclusively in fibroblasts in the adult mouse heart. Treatment of primary embryonic ventricular cell cultures with ISO (a nonselective β-adrenergic receptor agonist) increased CDK1 protein expression in fibroblasts and promoted their cell cycle activity. Quantitative PCR analysis confirmed that ISO increases CDK1 transcription in a transient manner. Further, the ISO-responsive element was mapped to the proximal - 100-bp sequence of the CDK1 promoter region using various 5=-flanking sequence deletion constructs. Sequence analysis of the - 100-bp CDK1 minimal promoter region revealed two putative nuclear factor-Y (NF-Y) binding elements. Overexpression of the NF-YA subunit in primary ventricular cultures significantly increased the basal activation of the - 100-bp CDK1 promoter construct but not the ISO-induced transcription of the minimal promoter construct. In contrast, dominant negative NF-YA expression decreased the basal activity of the minimal promoter construct and ISO treatment fully rescued the dominant negative effects. Furthermore, site-directed mutagenesis of the distal NF-Y binding site in the - 100-bp CDK1 promoter region completely abolished both basal and ISO-induced promoter activation of the CDK1 gene. Collectively, our results raise an exciting possibility that targeting CDK1 or NF-Y in the diseased heart may inhibit fibrosis and subsequently confer cardioprotection. [ABSTRACT FROM AUTHOR]

Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3′,5′-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, agerelated atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets. [ABSTRACT FROM AUTHOR]

The article focuses on the regulation of coronary blood flow during exercise. It states that the requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand, the heart rate, myocardial contractility and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met by augmenting coronary blood flow.

Examines whether endurance exercise training enhances liver level of heat shock protein (HSP) 70 and the contribution of HSP70 to hepatic protection against stress. Resting level of body weight, soleus citrate synthase activity and liver superoxide dismutase activity in sedentary and trained mice; Rectal temperature and liver thiobarubitric acid reactive substance of mice exposed to stresses; Inhibition of apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.

Studies the mechanisms of the interaction between an emotional load of swimming and metabolic capacity. Comparison of swim-elicited and Helox-elicited maximum oxygen consumption and hypothermia in mice of both lines acclimated to ambient cold, without affecting predisposition to or repeated swimming; Effect of between-line difference in swim maximum oxygen consumption on modulation of thermogenic capacities of mice by a swim stress-related mechanism.

Reducing body temperature of rodents has been found to improve their survival to ischaemia, hypoxia, chemical toxicants, and many other types of insults. Larger species, including humans, may also benefit from a lower body temperature when recovering from CNS ischaemia and other traumatic insults. Rodents subjected to these insults undergo a regulated hypothermic response (that is, decrease in set point temperature) characterised by preference for cooler ambient temperatures, peripheral vasodilatation, and reduced metabolic rate. However, forced hypothermia (that is, body temperature forced below set point) is the only method used in the study and treatment of human pathological insults. The therapeutic efficacy of the hypothermic treatment is likely to be influenced by the nature of the reduction in body temperature (that is, forced versus regulated). Homeostatic mechanisms counter forced reductions in body temperature resulting in physiological stress and decreased efficacy of the hypothermic treatment. On the other hand, regulated hypothermia would seem to be the best means of achieving a therapeutic benefit because thermal homeostatic systems mediate a controlled reduction in core temperature. [ABSTRACT FROM AUTHOR]

Sensitivity to the lethal effects of methamphetamine was observed under grouped conditions relative to isolated conditions in rats 25 and 30 days old but not in rats 7, 10, 15, or 20 days of age. Results are interpreted in terms of the development of the central catecholaminergic systems through which methamphetamine is thought to induce toxicity. [ABSTRACT FROM AUTHOR]