Effects of power training on muscle structure and neuromuscular performance.

The present study examines changes in muscle structure and neuromuscular performance induced by 15 weeks of power training with explosive muscle actions. Twenty-three subjects, including 10 controls, volunteered for the study. Muscle biopsies were obtained from the gastrocnemius muscle before and after the training period, while maximal voluntary isometric contractions (MVC) and drop jump tests were performed once every fifth week. No statistically significant improvements in MVC of the knee extensor (KE) and plantarflexor muscles were observed during the training period. However, the maximal rate of force development (RFD) of KE increased from 18,836+/-4282 to 25,443+/-8897 N (P<0.05) during the first 10 weeks of training. In addition, vertical jump height (vertical rise of the center of body mass) in the drop jump test increased significantly (P<0.01). Simultaneously, explosive force production of KE muscles measured as knee moment and power increased significantly; however, there was no significant change (P>0.05) in muscle activity (electromyography) of KE. The mean percentage for myosin heavy chain and titin isoforms, muscle fiber-type distributions and areas were unchanged. The enhanced performance in jumping as a result of power training can be explained, in part, by some modification in the joint control strategy and/or increased RFD capabilities of the KE.

Regulation of type IV collagen gene expression and degradation in fast and slow muscles during dexamethasone treatment and exercise.

Glucocorticoids have anti-anabolic effects on many tissues and can cause muscle atrophy. However, their effects on type IV collagen gene expression and degradation in skeletal muscle have not been studied previously. Rats were treated daily with dexamethasone or saline. Half the groups of experimental and control animals were also subjected to daily endurance or uphill running exercise to determine the possible preventive effects of exercise. After an experimental period of 3 or 10 days, the extensor digitorum longus, soleus and tibialis anterior muscles were studied. Dexamethasone treatment for 10 days reduced muscle weight and type IV collagen mRNA abundance in all muscles. Gene expression of matrix metalloproteinase-2 (MMP-2) was decreased in fast muscles. However, the effects of this decrease were possibly attenuated by the simultaneous decrease in the activity of tissue inhibitor of metalloproteinases (TIMP-2). The amount of type IV collagen was not changed during dexamethasone treatment or exercise. The regulation of type IV collagen degradation during dexamethasone treatment varied between slow and fast muscles. Although endurance running prevented muscle atrophy, exercise could not compensate the changes observed in the regulation of type IV collagen gene expression and degradation during dexamethasone treatment.

Effects of power training on mechanical efficiency in jumping.

The present study investigates the effects of power training on mechanical efficiency (ME) in jumping. Twenty-three subjects, including ten controls, volunteered for the study. The experimental group trained twice a week for 15 weeks performing various jumping exercises such as drop jumps, hurdle jumps, hopping and bouncing. In the maximal jumping test, the take-off velocity increased from 2.56 (0.24) m.s(-1) to 2.77 (0.18) m.s(-1) ( P<0.05). In the submaximal jumping of 50% of the maximum, energy expenditure decreased from 660 (110) to 502 (68) J.kg(-1).min(-1) ( P<0.001) while, simultaneously, ME increased from 37.2 (8.4)% to 47.4 (8.2)% ( P<0.001). Some muscle enzyme activities of the gastrocnemius muscle increased during the training period: citrate synthase from 35 (8) to 39 (7) micromol.g(-1) dry mass.min(-1) ( P<0.05) and beta-hydroxyacyl CoA dehydrogenase from 21 (4) to 23 (5) micromol.g(-1) dry mass.min(-1) ( P<0.05), whereas no significant changes were observed in phosphofructokinase and lactate dehydrogenase. In the control group, no changes in ME or in enzyme activities were observed. In conclusion, the enhanced performance capability of 8% in maximal jumping as a result of power training was characterized by decreased energy expenditure of 24%. Thus, the increased neuromuscular performance, joint control strategy, and intermuscular coordination (primary factors), together with improved aerobic capacity (secondary factor), may result in reduced oxygen demands and increased ME.

Synthesis and degradation of type IV collagen in rat skeletal muscle during immobilization in shortened and lengthened positions.

AIM: Type IV collagen is a major protein in basement membranes surrounding and supporting skeletal muscle cells. In the present study, we tested the hypotheses that immobilization down-regulates synthesis and up-regulates degradation of type IV collagen in skeletal muscle. METHODS: mRNA level and concentration of type IV collagen as well as mRNA levels and activities of proteins involved in its degradation were analysed from soleus (SOL), gastrocnemius (GAS) and extensor digitorum longus muscles after immobilization in shortened and lengthened positions for 1, 3 and 7 days. RESULTS: Following immobilization, type IV collagen mRNA level was decreased in SOL and GAS suggesting down-regulated synthesis of this protein. The mRNA level and activity of matrix metalloproteinase-2 (proMMP-2) were increased in all muscles, while the activity of tissue inhibitor of metalloproteinase-2 was decreased in SOL and GAS. These findings reflect an increased capacity for degradation of type IV collagen. CONCLUSIONS: As a consequence of decreased synthesis/degradation ratio immobilization reduced the concentration of type IV collagen in all muscles. The regulation of type IV collagen through synthesis and/or degradation seems, however, to be muscle specific. Immobilization in lengthened position seems to delay and partly decrease the net degradation of type IV collagen.

Regulation of synthesis of fibrillar collagens in rat skeletal muscle during immobilization in shortened and lengthened positions.

Immobilization has been shown to cause muscle atrophy and decreased total collagen synthesis in skeletal muscle. These changes can be counteracted by stretch. The purpose of this study was to find out the early effects of immobilization in shortened and lengthened positions on expression of type I and III collagen at pre- and post-translational level. The mRNA levels of type I and III collagen, prolyl 4-hydroxylase activity, total collagen concentration and the proportions of type I and III collagens were analysed in soleus (SOL), gastrocnemius (GM), extensor digitorum longus and tibialis anterior (TA) muscles during immobilization in shortened and lengthened positions for 1, 3 and 7 days. The mRNA levels for type I and III collagens decreased during 3-7 days in all muscles, except TA. In shortened GM and SOL, the mRNA level of type I collagen was lower than in the corresponding lengthened muscles. Prolyl 4-hydroxylase activity decreased in all muscles during 3-7 days. The activity in shortened GM was 30-37% lower than in the lengthened one during 3-7 days. Total collagen concentration and proportions of type I and III collagen showed no change during the 7-day immobilization period. The present study suggests that immobilization results in rapid down-regulation of total muscular collagen synthesis and that the timing and degree is roughly similar in type I and III collagens. Stretch seems to partially counteract these effects. Immobilization effect and the partially preventive effect of stretch on down-regulation of gene expression of prolyl 4-hydroxylase and fibrillar collagens during immobilization seems to be greater in weight-bearing SOL and GM than ankle joint dorsiflexors.

Protein targeting to the plasma membrane of adult skeletal muscle fiber: an organized mosaic of functional domains.

The plasma membrane of differentiated skeletal muscle fibers comprises the sarcolemma, the transverse (T) tubule network, and the neuromuscular and muscle-tendon junctions. We analyzed the organization of these domains in relation to defined surface markers, beta-dystroglycan, dystrophin, and caveolin-3. These markers were shown to exhibit highly organized arrays along the length of the fiber. Caveolin-3 and beta-dystroglycan/dystrophin showed distinct, but to some extent overlapping, labeling patterns and both markers left transverse tubule openings clear. This labeling pattern revealed microdomains over the entire plasma membrane with the exception of the neuromuscular and muscle-tendon junctions which formed distinct demarcated macrodomains. Our results suggest that the entire plasma membrane of mature muscle comprises a mosaic of T tubule domains together with sareolemmal caveolae and beta-dystroglycan domains. The domains identified with these markers were examined with respect to targeting of viral proteins and other expresseddomain-specific markers. We found that each marker protein was targeted to distinct microdomains. The macrodomains were intensely labeled with all our markers. Replacing the cytoplasmic tail of the vesicular stomatitis virus glycoprotein with that of CD4 resulted in retargeting from one domain to another. The domain-specific protein distribution at the muscle cell surface may be generated by targeting pathways requiring specific sorting information but this trafficking is different from the conventional apical-basolateral division.

Perfusion heterogeneity in human skeletal muscle: fractal analysis of PET data.

Muscle blood flow has been shown to be heterogeneous at the voxel by voxel level in positron emission tomography (PET) studies using oxygen-15 labelled water. However, the limited spatial resolution of the imaging device does not allow direct measurement of true vascular flow heterogeneity. Fractal dimension (D) obtained by fractal analysis describes the relationship between the relative dispersion and the size of the region studied, and has been used for the assessment of perfusion heterogeneity in microvascular units. This study was undertaken to evaluate fractal characteristics of PET perfusion data and to estimate perfusion heterogeneity in microvascular units. Skeletal muscle blood flow was measured in healthy subjects using [15O]water PET and the fractal characteristics of blood flow in resting and exercising skeletal muscle were analysed. The perfusion heterogeneity in microvascular units was estimated using the measured heterogeneity (relative dispersion, RD = SD/mean) and D values. Heterogeneity due to methodological factors was estimated with phantoms and subtracted from the flow data. The number of aggregated voxels was inversely correlated with RD both in phantoms (Pearson r = -0.96-0.97) and in muscle (Pearson r = -0.94) when both parameters were expressed using a logarithmic scale. Fractal dimension was similar between exercising (1.13) and resting (1.14) muscles and significantly lower than the values in the phantoms with different activity levels (1.27-1.29). Measured flow heterogeneity values were 20% +/- 6% (exercise) and 27% +/- 5% (rest, P < 0.001), whereas estimated flow heterogeneity values in microvascular units (1 mm3) were 35% +/- 14% (exercise) and 49% +/- 14% (rest, P < 0.01). In conclusion, these results show that it is feasible to apply fractal analysis to PET perfusion data. When microvascular flow heterogeneity is estimated using fractals, perfusion appears to be more heterogeneous in microvascular units than when obtained by routine spatial analysis of PET data. Analysis of flow heterogeneity using PET and fractals could provide new insight into physiological conditions and diseases associated with changes in peripheral vascular function.

Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content.

This experiment tested the hypothesis that running-induced damage to rat skeletal muscle causes changes in synthesis and degradation of basement membrane type IV collagen and to proteins regulating its degradation. Samples from soleus muscle and red and white parts of quadriceps femoris muscle (MQF) were collected 6 h or 1, 2, 4, or 7 days after downhill running. Increased muscle beta-glucuronidase activity indicated greater muscle damage in the red part of MQF than in the white part of MQF or soleus. In the red part of MQF, type IV collagen expression was upregulated at the pretranslational level and the protein concentration decreased, whereas matrix metalloproteinase-2 (MMP-2), a protein that degrades type IV collagen, and tissue inhibitor of metalloproteinase-2 (TIMP-2), a protein that inhibits degradation, were increased in parallel both at mRNA and protein levels. Type IV collagen mRNA level increased in the white part of MQF and soleus muscle. The protein concentration increased in the white part of MQF and was unchanged in soleus muscle. MMP-2 and TIMP-2 changed only slightly in the white part of MQF and soleus muscle. The changes seem to depend on the severity of myofiber injury and thus probably reflect reorganization of basement membrane compounds.

Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice.

Type XV collagen occurs widely in the basement membrane zones of tissues, but its function is unknown. To understand the biological role of this protein, a null mutation in the Col15a1 gene was introduced into the germ line of mice. Despite the complete lack of type XV collagen, the mutant mice developed and reproduced normally, and they were indistinguishable from their wild-type littermates. However, Col15a1-deficient mice showed progressive histological changes characteristic for muscular diseases after 3 months of age, and they were more vulnerable than controls to exercise-induced muscle injury. Despite the antiangiogenic role of type XV collagen-derived endostatin, the development of the vasculature appeared normal in the null mice. Nevertheless, ultrastructural analyses revealed collapsed capillaries and endothelial cell degeneration in the heart and skeletal muscle. Furthermore, perfused hearts showed a diminished inotropic response, and exercise resulted in cardiac injury, changes that mimic early or mild heart disease. Thus, type XV collagen appears to function as a structural component needed to stabilize skeletal muscle cells and microvessels.

Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running.

In the present study the release of proteins degrading extracellular matrix compounds to circulation was measured after damaging exercise in humans. Muscle damage was induced by downhill running; furthermore, the exercise was performed at both cold temperature (5 degrees C) and room temperature (22 degrees C) to study also the possible effect of environmental temperature on serum concentrations of matrix metalloproteinases MMP-2 and MMP-9, tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2, and MMP-2/TIMP-2 complex, and muscle damage monitored by serum creatine kinase measurements. Results were compared with those obtained from patients having rhabdomyolysis, myositis and Becker muscular dystrophy. The present study demonstrates an acute increase in serum concentrations of MMP-9, TIMP-1, and MMP-2/TIMP-2 complex, but no changes in serum MMP-2 concentrations in response to eccentric exercise. Serum creatine kinase activity data suggest greater muscle damage after downhill running in a cold environment than at room temperature. The present observations about at most slight changes in serum MMP and TIMP concentrations and lack of their correlation to increased serum creatine kinase after exercise indicate that serum measurements of MMPs and TIMPs do not sensitively respond to exercise induced skeletal muscle damage and extracellular matrix regeneration. On the other hand, severe skeletal muscle damage, such as rhabdomyolysis, myositis and Becker muscular dystrophy, seemed to have an effect on serum MMP and TIMP concentrations.

Biochemical composition of muscle extracellular matrix: the effect of loading.

Collagen plays an important role in skeletal muscle both during muscle differentiation and normal muscle growth, and also serves a role as a supportive structure. It is the most abundant protein of the extracellular matrix and of the 19 distinct collagen types, types I, III, IV and V are the dominating ones in skeletal muscle. Both collagen synthesis as well as degradation is influenced by either physical loading or immobilization in skeletal muscle, and recent methods have allowed for greater understanding of the posttranslational processing of collagen.

Elevated protein content and prolyl 4-hydroxylase activity in severely degenerated human annulus fibrosus.

Alterations involved with the intervertebral disc degeneration are partly well described, however, it is not so well known how collagen network is affected by the disease. We analyzed the rate of collagen biosynthesis (estimated by the enzymic activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase) and the level of hydroxylysylpyridinoline and lysylpyridinoline crosslinks both in normal (n=7) and degenerated (n=7) human annulus fibrosus. The activity of prolyl 4-hydroxylase was significantly increased in degenerated tissue. However, no significant changes in the collagen content or in the amount of hydroxylysylpyridinoline and lysylpyridinoline collagen crosslinks were observed. On the other hand, the content of soluble proteins was significantly increased. Our results suggest that collagen biosynthesis is increased in degenerated human annulus fibrosus, obviously to compensate the impairment of collagen fibers. The faster turnover of collagen in degenerated annulus fibrosus, suggested by the increased prolyl 4-hydroxylase activity and unchanged collagen content, seems not to cause any significant changes in its mature pyridinium crosslink concentrations.

Type IV collagen and its degradation in paralyzed human muscle: effect of functional electrical stimulation.

The purpose of this study was to evaluate the effects of spinal cord injury (SCI) and functional electrical stimulation (FES) of paralyzed muscles on type IV collagen content and proteins involving its degradation, which is initiated by matrix metalloproteinase (MMP)-2 and -9 and regulated by their tissue inhibitors (TIMPs)-2 and -1. Ten SCI subjects participated in an 18-month program of functional electrical stimulation (FES) of their leg muscles. Needle biopsies were taken from the vastus lateralis muscle before and at various times during the training period, and from able-bodied controls. Type IV collagen concentration was unaltered. ProMMP-2 level of SCI subjects before the training period tended to be higher than able-bodied controls and was significantly above the control level after FES. MMP-9 concentration was unchanged. The results suggest accelerated type IV collagen turnover in skeletal muscle of SCI individuals especially after FES as a part of adaptive process of the muscle.

mRNA levels for alpha-subunit of prolyl 4-hydroxylase and fibrillar collagens in immobilized rat skeletal muscle.

There is evidence that immobilization causes a decrease in total collagen synthesis in skeletal muscle within a few days. In this study, early immobilization effects on the expression of prolyl 4-hydroxylase (PH) and the main fibrillar collagens at mRNA and protein levels were investigated in rat skeletal muscle. The right hindlimb was immobilized in full plantar flexion for 1, 3, and 7 days. Steady-state mRNAs for alpha- and beta-subunits of PH and type I and III procollagen, PH activity, and collagen content were measured in gastrocnemius and plantaris muscles. Type I and III procollagen mRNAs were also measured in soleus and tibialis anterior muscles. The mRNA level for the PH alpha-subunit decreased by 49 and 55% (P < 0.01) in gastrocnemius muscle and by 41 and 39% (P < 0.05) in plantaris muscle after immobilization for 1 and 3 days, respectively. PH activity was decreased (P < 0.05-0.01) in both muscles at days 3 and 7. The mRNA levels for type I and III procollagen were decreased by 26-56% (P < 0.05-0.001) in soleus, tibialis anterior, and plantaris muscles at day 3. The present results thus suggest that pretranslational downregulation plays a key role in fibrillar collagen synthesis in the early phase of immobilization-induced muscle atrophy.

Increased mRNAs for procollagens and key regulating enzymes in rat skeletal muscle following downhill running.

The purpose of the study was to investigate pre-translational regulation of collagen expression after a single bout of exercise. We analysed steady-state messenger ribonucleic acid (mRNA) levels for collagen types I, III and IV, alpha- and beta-subunits of prolyl 4-hydroxylase and lysyl oxidase (enzymes modifying procollagen chains), and enzyme activity of prolyl 4-hydroxylase from rat soleus muscle (MS) and the red parts of quadriceps femoris muscle (MQF) after 12 h and after 1, 2, 4, 7 and 14 days of downhill (-13.5 degrees ) treadmill running at a speed of 17 m.min-1 for 130 min. Histological and biochemical assays revealed exercise-induced muscle damage in MQF but not MS. Steady-state mRNA levels for the alpha- and beta-subunits of prolyl 4-hydroxylase in MQF, lysyl oxidase in MS and MQF were increased 12 h after running, whereas prolyl 4-hydroxylase activity did not increase until 2 days after exercise. The mRNA levels for the fibrillar collagens (I and III) and basement membrane type IV collagen significantly increased 1 day and 12 h after exertion, respectively. Peak mRNA levels were observed 2-4 days after running, the increases being more pronounced in MQF than in MS. No significant changes were observed in types I or III collagen at the protein level. Strenuous downhill running thus causes an increase in gene expression for collagen types I and III and their post-translational modifying enzymes in skeletal muscle in a co-ordinated manner. These changes, together with the increased gene expression of type IV collagen, may represent the regenerative response of muscle extracellular matrix to exercise-induced injury and an adaptive response to running exertion.

Gender differences in skeletal muscle fibre damage after eccentrically biased downhill running in rats.

Specific antibodies against structural proteins of muscle fibres (actin, desmin, dystrophin) and extracellular matrix (fibronectin) were used to study the effect of eccentrically biased downhill running exercise (13,5 degrees, 17 m min(-1), 130 min) on the magnitude and properties of myofibre injury in the quadriceps femoris muscle of male and female rats. Muscle beta-glucuronidase activity, a quantitative indicator of muscle damage, showed clearly smaller increase in female than in male rats during the 4-day period following exercise. A similar course of histopathological changes was observed in both sexes, although females showed slower and less marked changes than males. In males, discontinuous or even lost submembrane protein dystrophin staining was observed in some swollen fibres immediately after exercise, before the loss of desmin and staining of disorganized actin, i.e. before the disruption of the cytoskeletal system and the contractile apparatus. The observation that no dramatic changes in the microarchitecture of the muscle fibres were detected immediately or even 6 h after the exercise in females compared with males may indicate that the sarcolemma of the females might be strengthened against membrane damage by a still unknown stabilizing compound.

The disruption of myofibre structures in rat skeletal muscle after forced lengthening contractions.

Specific antibodies against structural proteins (actin, desmin, dystrophin, fibronectin) of muscle fibres were used to study the effect of forced lengthening contractions on muscle microarchitecture. Tibialis anterior (TA) muscle of male Wistar rats were subjected to 240 forced lengthening contractions. At consecutive time points (0, and 6 h, 2, 4, and 7 days) after stimulation, the TA muscle was excised for biochemical and histological assays. Beta-Glucuronidase activity, a quantitative indicator of muscle damage, showed increased values 2-7 days after the lengthening, peaking on day 4 (11.7-fold increase). A typical course of histopathological changes (myofibre swelling, necrosis and regeneration) was observed. In immunohistochemistry, the earliest abnormality observed was discontinuous dystrophin staining in some swollen fibres immediately after commencement of exercise, while at the same time no alterations occurred in the staining of the other antibodies studied. Six hours later, all the swollen fibres were uniformly desmin as well as dystrophin negative. The great majority, but not all, of the swollen fibres showed disorganized actin staining and intramyocellular localization of fibronectin. The early phase disruption of myofibre structures as measured in this study provides evidence of their central role following damage in skeletal muscle. These results suggest that the sequence of structural changes in the route to muscle fibre necrosis in injury induced by forced lengthening contraction originates in the disruption of the plasma membrane and the intermediate filament, which leads to disturbances in the myofibrillar system.

Muscle damage induced by stretch-shortening cycle exercise.

PURPOSE: Strenuous stretch-shortening cycle exercise was used as a model to study the leakage of proteins from skeletal muscle. METHODS: The analysis included serum levels of creatine kinase (S-CK), myoglobin (S-Mb), and carbonic anhydrase (S-CA III). Blood samples from power- (N=11) and endurance-trained (N=10) athletes were collected before, 0, and 2 h after the exercise, which consisted of a total of 400 jumps. RESULTS: The levels of all determined myocellular proteins increased immediately after the exercise (P < 0.05-0.001) among both subject groups. In the endurance group, the protein levels increased (P < 0.05-0.001) further during the following 2 h after the exercise, and the ratio of S-CA III and S-Mb decreased (P < 0.05) in a before-after comparison. This was not the case among the power group despite their greater mechanical work (P < 0.001) and higher ratio of eccentric and concentric EMG activity of the leg extensor muscles (P < 0.05). CONCLUSIONS: The differences of the determined protein levels between the subject groups might be due to obvious differences in the muscle fiber distribution, differences in recruitment order of motor units, and/or differences in training background.

Induction of cardiac natriuretic peptide gene expression in rats trained in hypobaric hypoxic conditions.

Adaptation of cardiac muscle to prolonged hypobaric hypoxia (770-740 mbar, 2,250-2,550 m), endurance training, and their combination was studied in rats by investigating the gene expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in atria and ventricles. Rats were assigned into the following groups according to the barometric conditions and physical activity; normobaric sedentary (NS), normobaric training, hypobaric sedentary (HS), and hypobaric training (HT). Experimental periods were 10, 21, and 56 days; the groups at 91 days served as recovery groups from exposure to and training in normobaric and hypobaric conditions for 56 days. The right ventricular hypertrophy in HT rats at 10 days and 56 days was associated with elevated BNP mRNA levels (2.1- and 1.7-fold, P < 0.05, respectively), whereas hypobaric exposure without training was not sufficient to significantly increase ventricular BNP gene expression, although it lead to hypertrophy of the right ventricle. Right and left atrial BNP mRNA levels were also increased (up to 3.9-fold, P < 0.01) in 10-day HS and 10-day HT groups. ANP mRNA levels in right ventricle and left ventricular epicardium were over twofold higher (P < 0.05-0.01) in 10-day HS and 10-day HT groups in comparison to 10-day NS group. Plasma immunoreactive ANP concentration was increased (P < 0.05) in both hypobaric groups up to 21 days. The results show that exposure to hypobaric hypoxia itself and endurance training in hypobaric, hypoxic conditions lead to a marked early increase in ventricular and atrial ANP and BNP mRNA levels. The adaptational response to hypoxia was more pronounced when the oxygen availability was lowered additionally by endurance training carried out in hypobaric hypoxic conditions.

Right ventricular collagen type III and IV gene expression increases during early phases of endurance training in hypobaric hypoxic condition.

The objective of this study was to examine the effects of prolonged exposure to hypobaric hypoxic condition, physical training and their combination on collagen type I, III and IV gene expression in the ventricles and atria of rat heart. Male rats were assigned to four groups: normobaric sedentary (NS) and trained (NT), and hypobaric sedentary (HS) and trained (HT). Exposure to and treadmill running training in hypobaric condition were carried out in a hypobaric chamber (770-740 mbar, 2250-2550 m). Experimental periods were 10, 21 and 56 days; the groups of 91 days served as recovery groups from experimental settings of 56 days. Exposure to hypobaric condition as such and in combination with endurance training for 10 days increased right ventricular weight-to-body weight ratio (RV/BW) by 26% (p < 0.001) and 23% (p < 0.01), respectively, when compared to 10NS. RV/BW was significantly increased also in 21HT and 56HT. Left ventricular weight-to-body weight ratio was 13% (p < 0.01) and 14% (p < 0.01) higher in 21HT and 56HT, respectively, than in the respective NS. Right ventricular collagen type III mRNA level was 33% (p = 0.065) and 38% (p < 0.01) higher in 10HT than in 10NS and 10NT, respectively. Right ventricular collagen type IV mRNA level was 29% (p < 0.001) higher in 10HT than in 10NS. Relatively slight left ventricular hypertrophy was not associated with significant changes in collagen mRNA levels. Decreased left ventricular subepicardial prolyl 4-hydroxylase activity in 10HS and 10HT suggests transient corresponding decrease in the rate of collagen synthesis. This study shows that combination of endurance training and moderate hypobaric hypoxic condition leads to increased right ventricular collagen type III and IV gene expression associated with right ventricular hypertrophy.