Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training

McCall, G. E., W. C. Byrnes, A. Dickinson, P. M. Pattany,and S. J. Fleck. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.J. Appl. Physiol. 81(5):2004-2012, 1996.Twelve male subjects with recreationalresistance training backgrounds completed 12 wk of intensifiedresistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groupswere trained, with four exercises emphasizing the forearm flexors.After training, strength (1-repetition maximum preacher curl) increasedby 25% (P < 0.05). Magneticresonance imaging scans revealed an increase in the biceps brachiimuscle cross-sectional area (CSA) (from 11.8 ± 2.7 to 13.3 ± 2.6 cm²;n = 8;P < 0.05). Muscle biopsies of thebiceps brachii revealed increases(P < 0.05) in fiber areas for type I(from 4,196 ± 859 to 4,617 ± 1,116 µm²;n = 11) and II fibers (from 6,378 ± 1,552 to 7,474 ± 2,017 µm²;n = 11). Fiber number estimated fromthe above measurements did not change after training (293.2 ± 61.5 × 10³ pretraining; 297.5 ± 69.5 × 10³ posttraining;n = 8). However, the magnitude ofmuscle fiber hypertrophy may influence this response because thosesubjects with less relative muscle fiber hypertrophy, but similarincreases in muscle CSA, showed evidence of an increase in fibernumber. Capillaries per fiber increased significantly(P < 0.05) for both type I(from 4.9 ± 0.6 to 5.5 ± 0.7;n = 10) and II fibers (from 5.1 ± 0.8 to 6.2 ± 0.7; n = 10). Nochanges occurred in capillaries per fiber area or muscle area. Inconclusion, resistance training resulted in hypertrophy of the totalmuscle CSA and fiber areas with no change in estimated fiber number,whereas capillary changes were proportional to muscle fiber growth.

     

Increased capillarity in leg muscle of finches living at altitude

An increased ratio of muscle capillary tofiber number (capillary/fiber number) at altitude has been found inonly a few investigations. The highly aerobic pectoralismuscle of finches living at 4,000-m altitude(Leucosticte arctoa; A) was recentlyshown to have a larger capillary/fiber number and greater contributionof tortuosity and branching to total capillary length than sea-levelfinches (Carpodacus mexicanus; SL) ofthe same subfamily (O. Mathieu-Costello, P. J. Agey, L. Wu, J. M. Szewczak, and R. E. MacMillen. Respir. Physiol. 111: 189-199, 1998). To evaluate the roleof muscle aerobic capacity on this trait, we examined the less-aerobicleg muscle (deep portion of anterior thigh) in the same birds. We foundthat, similar to pectoralis, the leg muscle in A finches had a greater capillary/fiber number (1.42 ± 0.06) than that in SLfinches (0.77 ± 0.05; P < 0.01),but capillary tortuosity and branching were not different. As alsofound in pectoralis, the resulting larger capillary/fiber surface in Afinches was proportional to a greater mitochondrial volume permicrometer of fiber length compared with that in SL finches. Theseobservations, in conjunction with a trend to a greater (rather thansmaller) fiber cross-sectional area in A than in SL finches (A: 484 ± 42, SL: 390 ± 26 µm²,both values at 2.5-µm sarcomere length;P = 0.093), support the notion thatchronic hypoxia is also a condition in which capillary-to-fiber structure is organized to match the size of the musclecapillary-to-fiber interface to fiber mitochondrial volume rather thanto minimize intercapillary O₂diffusion distances.

     

Training-induced alterations in young and senescent rat diaphragm muscle.

The current study sought to examine the effects of chronic endurance treadmill running on oxidative capacity and capillary density in specific diaphragm muscle fiber types in young (5 mo) and senescent (greater than or equal to 23 mo) female Fischer 344 rats. Both young and senescent animals trained at approximately 75% of maximal O2 consumption for 1 h/day 5 days/wk for 10 wk. Plantaris citrate synthase activity was significantly increased (P less than 0.01) in both young and old trained groups. Densitometric analysis of succinate dehydrogenase (SDH) activity in diaphragm type I, IIa, and IIb muscle fibers was done using a computerized image-processing system. There were no age-related differences in SDH activity between the young and old groups for any of the fiber types. In addition, SDH activity was found to be significantly increased (P less than 0.05) in all three fiber types in both the young and senescent trained animals compared with their sedentary counterparts. Fiber size and capillary density did not differ between young and senescent rats, nor did exercise affect this measure. Each fiber, irrespective of type, had an average of approximately four capillaries in contact with it. However, type IIb fibers had a significantly lower capillary density per unit area than type I or IIa muscle fibers. The results indicate that the senescent costal diaphragm maintains its ability to adapt to an increased metabolic demand brought about by locomotor exercise. Of further interest is the finding that training adaptations occurred in all three fiber types, suggesting that increased work of breathing from moderate exercise leads to recruitment of all three fiber types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women.

Previous studies of endurance exercise training in older men and women generally have found only minimal skeletal muscle adaptations to training. To evaluate the possibility that this may have been due to an inadequate training stimulus, we studied 23 healthy older (64 +/- 3 yr) men and women before and after they had trained by walking/jogging at 80% of maximal heart rate for 45 min/day 4 days/wk for 9-12 mo. This training program resulted in a 23% increase in maximal O2 consumption. Needle biopsy samples of the lateral gastrocnemius muscle were obtained before and after training and analyzed for selected histochemical and enzymatic characteristics. The percentage of type I muscle fibers did not change with training. The percentage of type IIb fibers, however, decreased from 19.1 +/- 9.1 to 15.1 +/- 8.1% (P less than 0.001), whereas the percentage of type IIa fibers increased from 22.1 +/- 7.7 to 29.6 +/- 9.1% (P less than 0.05). Training also induced increases in the cross-sectional area of both type I (12%; P less than 0.001) and type IIa fibers (10%; P less than 0.05). Capillary density increased from 257 +/- 43 capillaries/mm2 before training to 310 +/- 48 capillaries/mm2 after training (P less than 0.001) because of increases in the capillary-to-fiber ratio and in the number of capillaries in contact with each fiber. Lactate dehydrogenase activity decreased by 21% (P less than 0.001), whereas the activities of the mitochondrial enzymes succinate dehydrogenase, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase increased by 24-55% in response to training (P less than 0.001-0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Myosin heavy chain mRNA transform to faster isoforms in immobilized skeletal muscle: a quantitative PCR study

Jänkälä, Heidi, Veli-Pekka Harjola, NielsErik Petersen, and Matti Härkönen. Myosin heavy chainmRNA transform to faster isoforms in immobilized skeletal muscle: aquantitative PCR study. J. Appl.Physiol. 82(3): 977-982, 1997.A quantitative polymerase chain reaction (PCR) method was used to measure the quantities of type I, IIa, IIx, and IIb myosin heavy chain (MHC) mRNAin total RNA preparations of the soleus, gastrocnemius, and plantarismuscles of normal and hindlimb-immobilized rats. Type IIx and even typeIIb MHC mRNA were demonstrated at extremely low levels in normalsoleus, 2.1 ± 0.4 × 10⁵and 5.0 ± 0.2 × 10⁵molecules of mRNA per microgram total RNA, respectively. Immobilization for 1 wk significantly altered the gene expression of MHC isoforms. Insoleus, both type IIx and IIb MHC genes became significantly upregulated, 24-fold (P < 0.005) and 2.6-fold (P < 0.05),respectively. In gastrocnemius, the level of type IIa MHC mRNAdecreased by 51% (P < 0.01) and thelevel of type IIx MHC mRNA increased by 140%(P < 0.05). In plantaris, the levelof type IIa MHC mRNA decreased by 58%(P < 0.005). In conclusion,immobilization changed the MHC mRNA profile in three different types ofskeletal muscle toward faster isoforms. The quantitative results permitreliable evaluation of changes in mRNA levels.

     

Time course of changes in capillarization in hypertrophied rat plantaris muscle

The time course of angiogenesis duringhypertrophy of the rat plantaris muscle was studied by using aunilateral, synergistic ablation model. Animals(n = 6/group) were euthanized 2, 5, 7, 15, 21, and 30 days postmyectomy. Sections from both thehypertrophied and contralateral muscles were simultaneouslystained for capillaries and muscle fiber type. Mean fibercross-sectional area (FA) and various indexes of capillarity weredetermined by using a video analysis system. The capillary supplyto individual fibers, assessed as the FA supplied per capillarycontact, remained unchanged until day21 (compared with day2) and exhibited a significant increase atday 30. Analysis of the time course ofcapillary development on the basis of the number of capillary contactsper fiber, and of hypertrophy on the basis of FA, yielded half-lives of10.1 and 11.2 days, respectively. It was concluded that angiogenesis during muscle overload is tightly coupled to the changes in FA, whichcould suggest that the two processes are initiated and/or driven by some common factor(s).

     

Capillary growth in relation to blood flow and performance in overloaded rat skeletal muscle

Rat extensor digitorum longus muscleswere overloaded by stretch after removal of the synergist tibialisanterior muscle to determine the relationship between capillary growth,muscle blood flow, and presence of growth factors. After 2 wk,sarcomere length increased from 2.4 to 2.9 µm. Capillary-to-fiberratio, estimated from alkaline phosphatase-stained frozen sections, wasincreased by 33% (P < 0.0001) and60% (P < 0.01), compared withcontrol muscles (1.44 ± 0.06) after 2 and 8 wk, respectively. At 2 wk, the increased capillary-to-fiber ratio was not associated with anychanges in mRNA for basic fibroblast growth factor (FGF-2) or itsprotein distribution. FGF-2 immunoreactivity was present in nerves andlarge blood vessels but was negative in capillaries, whereas theactivity of low-molecular endothelial-cell-stimulating angiogenicfactor (ESAF) was 50% higher in stretched muscles. Muscle blood flowsmeasured by radiolabeled microspheres during contractions were notsignificantly different after 2 or 8 wk (132 ± 37 and 177 ± 22 ml · min¹ · 100 g¹, respectively) fromweight-matched controls (156 ± 12 and 150 ± 10 ml · min¹ · 100 g¹, respectively).Resistance to fatigue during 5-min isometric contractions (final/peaktension × 100) was similar in 2-wk overloaded and contralateralmuscles (85 vs. 80%) and enhanced after 8 wk to 92%, compared with77% in contralateral muscles and 67% in controls. We conclude thatincreased blood flow cannot be responsible for initiating expansion ofthe capillary bed, nor does it explain the reduced fatigue withinoverloaded muscles. However, stretch can present a mechanical stimulusto capillary growth, acting either directly on the capillary abluminalsurface or by upregulating ESAF, but not FGF-2, in the extracellular matrix.

     

Contractile function of single muscle fibers after hindlimb unweighting in aged rats

Thompson, L. V., and J. A. Shoeman. Contractilefunction of single muscle fibers after hindlimb unweighting in aged rats. J. Appl. Physiol. 84(1):229-235, 1998.This investigation determined how muscle atrophyproduced by hindlimb unweighting (HU) alters the contractile functionof single muscle fibers from older animals (30 mo). After 1 wk of HU,small bundles of fibers were isolated from the soleus muscles and thedeep region of the lateral head of the gastrocnemius muscles. Singleglycerinated fibers were suspended between a motor lever and forcetransducer, functional properties were studied, and the myosin heavychain (MHC) composition was determined electrophoretically. After HU, the diameter of type I MHC fibers of the soleus declined (88 ± 2 vs. 80 ± 4 µm) and reductions were observed in peak active force (47 ± 3 vs. 28 ± 3 mg) and peak specific tension(P_o; 80 ± 5 vs. 56 ± 5 kN/m²). The maximal unloadedshortening velocity increased. The type I MHC fibers from thegastrocnemius showed reductions in diameter (14%), peak active force(41%), and P_o (24%), whereas thetype IIa MHC fibers showed reductions in peak active force andP_o. Thus 1 wk ofinactivity has a significant effect on the force-generating capacity ofsingle skeletal muscle fibers from older animals in a fibertype-specific manner (type I MHC > type IIa MHC > type I-IIa MHC).The decline in the functional properties of single skeletal musclefibers in the older animals appears to be more pronounced than what hasbeen reported in younger animal populations.

     

Extreme endurance training and fiber type adaptation in rat diaphragm

Extreme endurance training was used to investigate the adaptability of the rat diaphragm muscle fibers. During the final phase of the 14-wk training program, the animals were running for 240 min/day at an estimated requirement of 80% of pretraining maximal O2 consumption. Analysis of a sample of the costal diaphragm indicated that training resulted in a 34% reduction (P less than 0.05) in the percent distribution of type IIa fibers [27.7 +/- 1.1 vs. 18.3 +/- 2.6 (SE)] and a 15% increase (P less than 0.05) in the percent of type IIb fibers (40.0 +/- 1.2 vs. 46.1 +/- 2.4). No change (P greater than 0.05) was found in the distribution of the type I fibers (32.3 +/- 1.2 vs. 35.7 +/- 1.3). Oxidative potential as assessed with NADH-tetrazolium reductase and measured microphotometrically increased (P less than 0.05) by 19% in type I fibers but did not change in either the type IIa or type IIb fibers. No effect of training was found when a different oxidative marker, succinic dehydrogenase, was employed. Similarly glycolytic potential based on the activity of alpha-glycerophosphate dehydrogenase was not affected by training. Glycogen concentration was elevated by 60% (P less than 0.01) in type I fibers and 77% (P less than 0.01) in type IIb fibers with training but was not altered (P greater than 0.05) in type IIa fibers. Reductions (P less than 0.05) in fiber area ranging from 11 to 20% were observed in all fiber types as a result of training, whereas the number of capillaries per fiber remained static.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alignment of microvascular units along skeletal muscle fibers of hamster retractor

Emerson, Geoffrey G., and Steven S. Segal. Alignment ofmicrovascular units along skeletal muscle fibers of hamster retractor.J. Appl. Physiol. 82(1): 42-48, 1997.When muscle fibers contract, blood flow requirements increasealong their entire length. However, the organization of capillaryperfusion along muscle fibers is unclear. The microvascular unit (MVU)is defined as a terminal arteriole and the group of capillaries itsupplies. We investigated whether neighboring MVUs along the fiber axis perfused the same group of muscle fibers by using the parallel-fibered retractor muscle. Hamsters were anesthetized and perfused with Microfilto visualize MVUs relative to muscle fibers. Fields of study, whichencompassed five to seven neighboring MVUs along a muscle fiber, werechosen from the interior of muscles and along muscle edges. On average,MVUs were 1 mm in length, 0.50 mm in width, and 0.1 mm deep; segmentsof ~30 fibers were contained in this tissue volume of 0.05 mm³ (20 MVUs/mg muscle). The totaldistance across muscle fibers encompassed by a pair of MVUs isdesignated "union" (U); the fraction of this distance common toboth MVUs is designated "intersection" (I). The ratio of I to Ufor the widths of neighboring MVUs provides an index of MVU alignmentalong muscle fibers (e.g., I/U = 1.0 indicates complete alignment,where the fibers perfused by one MVU are the same as those perfused bythe neighboring MVU). We found that I/U along muscle edges (0.71 ± 0.02) was greater (P < 0.05) thanthe ratio measured within muscles (0.66 ± 0.02). A model predicteda maximum I/U of 0.58 with random MVU alignment. Thus measured valueswere closer to random than to complete alignment. These findingsindicate that an increase in blood flow along muscle fibers requiresthe perfusion of many MVUs and imply that vasodilation is coordinatedamong the parent arterioles from which corresponding MVUsarise.

     

Skeletal muscle adaptations in response to voluntary wheel running in myosin heavy chain null mice.

10.1152/ japplphysiol.00832.2001.-To examine the effects of gene inactivation on the plasticity of skeletal muscle, mice null for a specific myosin heavy chain (MHC) isoform were subjected to a voluntary wheel-running paradigm. Despite reduced running performance compared with nontransgenic C57BL/6 mice (NTG), both MHC IIb and MHC IId/x null animals exhibited increased muscle fiber size and muscle oxidative capacity with wheel running. In the MHC IIb null animals, there was no significant change in the percentage of muscle fibers expressing a particular MHC isoform with voluntary wheel running at any time point. In MHC IId/x null mice, wheel running produced a significant increase in the percentage of fibers expressing MHC IIa and MHC I and a significant decrease in the percentage of fibers expressing MHC IIb. Muscle pathology was not affected by wheel running for either MHC null strain. In summary, despite their phenotypes, MHC null mice do engage in voluntary wheel running. Although this wheel-running activity is lessened compared with NTG, there is evidence of distinct patterns of muscle adaptation in both null strains.     

Anabolic steroids in part reverse glucocorticoid-induced alterations in rat diaphragm

Animal and clinical studies have shownrespiratory muscle dysfunction caused by treatment withglucocorticoids. The present study was designed to investigate whetheranabolic steroids are able to antagonize the loss of diaphragm forceinduced by long-term low-dose methylprednisolone (MP) administration.Male adult rats were randomized to receive saline or MP (0.2 mg · kg¹ · day¹sc) during 9 mo, with or without nandrolone decanoate (ND; 1 mg · kg¹ · wk¹im) during the last 3 mo. The ~10% reduction in force generation ofisolated diaphragm bundles induced by MP was completely abolished byaddition of ND. The MP-induced decrease in number of fibers expressingtype IIb myosin heavy chains was not reversed by ND. MP slightlyreduced type I, IIa, and IIx fiber cross-sectional areas(CSA), but not type IIb fiber CSA. Addition of ND abolished thereduction in IIa and IIx fiber CSA. The MP-induced alterations inglycogenolytic activity and fatty acid oxidation capacity were notreversed by ND. In conclusion, the marked reduction in diaphragm forcecaused by long-term low-dose MP was completely abolished by addition ofND. ND in part also antagonized the effects of MP on diaphragmmorphology but showed no beneficial effects on biochemical changes.

     

Skeletal muscle fiber quality in older men and women

Wholemuscle strength and cross-sectional area (WMCSA), andcontractile properties of chemically skinned segments from single fibers of the quadriceps were studied in 7 young men (YM, 36.5 ± 3.0 yr), 12 older men (OM, 74.4 ± 5.9 yr), and 12 olderwomen (OW, 72.1 ± 4.3 yr). WMCSA was smaller in OMcompared with YM (56.1 ± 10.1 vs. 79.7 ± 13.1 cm²; P = 0.031) and in OW (44.9 ± 7.5; P < 0.003) compared with OM. Age-related, but notsex-related, differences in strength were eliminated after adjustingfor WMCSA. Maximal force was measured in 552 type I and 230 type IIAfibers. Fibers from YM (type I = 725 ± 221; type IIA = 792 ± 271 µN) were stronger (P < 0.001) thanfibers from OM (I = 505 ± 179; IIA = 577 ± 262 µN) even after correcting for size. Type IIA fibers were stronger(P < 0.005) than type I fibers in YM and OM but not inOW (I = 472 ± 154; IIA = 422 ± 97 µN).Sex-related differences in type I and IIA fibers were dependent onfiber size. In conclusion, differences in WMCSA explain age-relateddifferences in strength. An intrinsic defect in contractile proteinscould explain weakness in single fibers from OM. Sex-relateddifferences exist at the whole muscle and single fiber levels.

     

Effect of P(i) on unloaded shortening velocity of slow and fast mammalian muscle fibers

Chemically skinned muscle fibers,prepared from the rat medial gastrocnemius and soleus, were subjectedto four sequential slack tests in Ca²⁺-activating solutionscontaining 0, 15, 30, and 0 mM added P_i. P_i (15 and 30 mM) had no effect on the unloaded shortening velocity (V_o) of fibers expressing type IIb myosin heavychain (MHC). For fibers expressing type I MHC, 15 mM P_i didnot alter V_o, whereas 30 mM P_ireduced V_o to 81 ± 1% of the original 0 mM P_i value. This effect was readily reversible whenP_i was lowered back to 0 mM. These results are notcompatible with current cross-bridge models, developed exclusively fromdata obtained from fast fibers, in which V_o isindependent of P_i. The response of the type I fibers at 30 mM P_i is most likely the result of increased internal drag opposing fiber shortening resulting from fiber type-specific effects ofP_i on cross bridges, the thin filament, or therate-limiting step of the cross-bridge cycle.

     

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

Delp, Michael D., Changping Duan, John P. Mattson, andTimothy I. Musch. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure.J. Appl. Physiol. 83(4):1291-1299, 1997.One of the primary consequences of leftventricular dysfunction (LVD) after myocardial infarction is adecrement in exercise capacity. Several factors have been hypothesizedto account for this decrement, including alterations in skeletal musclemetabolism and aerobic capacity. The purpose of this study was todetermine whether LVD-induced alterations in skeletal muscle enzymeactivities, fiber composition, and fiber size are1) generalized in muscles orspecific to muscles composed primarily of a given fiber type and2) related to the severity of theLVD. Female Wistar rats were divided into three groups: sham-operatedcontrols (n = 13) and rats withmoderate (n = 10) and severe(n = 7) LVD. LVD was surgicallyinduced by ligating the left main coronary artery and resulted inelevations (P < 0.05) in leftventricular end-diastolic pressure (sham, 5 ± 1 mmHg; moderate LVD,11 ± 1 mmHg; severe LVD, 25 ± 1 mmHg). Moderate LVDdecreased the activities of phosphofructokinase (PFK) and citratesynthase in one muscle composed of type IIB fibers but did not modifyfiber composition or size of any muscle studied. However, severe LVDdiminished the activity of enzymes involved in terminal and-oxidation in muscles composed primarily of type I fibers, type IIAfibers, and type IIB fibers. In addition, severe LVD induced areduction in the activity of PFK in type IIB muscle, a 10% reductionin the percentage of type IID/X fibers, and a corresponding increase inthe portion of type IIB fibers. Atrophy of type I fibers, type IIAfibers, and/or type IIB fibers occurred in soleus and plantarismuscles of rats with severe LVD. These data indicate that rats withsevere LVD after myocardial infarction exhibit1) decrements in mitochondrialenzyme activities independent of muscle fiber composition,2) a reduction in PFK activity in type IIB muscle, 3) transformationof type IID/X to type IIB fibers, and4) atrophy of type I, IIA, and IIBfibers.

     

Regional differences in expression of VEGF mRNA in rat gastrocnemius following 1 hr exercise or electrical stimulation

Background  

Vascular endothelial growth factor (VEGF) mRNA levels increase in rat skeletal muscle after a single bout of acute exercise. We assessed regional differences in VEGF₁₆₅ mRNA levels in rat gastrocnemius muscle using in situ hybridization after inducing upregulation of VEGF by treadmill running (1 hr) or electrical stimulation (1 hr). Muscle functional regions were defined as oxidative (primarily oxidative fibers, I and IIa), or glycolytic (entirely IIb or IId/x fibers). Functional regions were visualized on muscle cross sections that were matched in series to slides processed through in situ hybridization with a VEGF₁₆₅ probe. A greater upregulation in oxidative regions was hypothesized.     

Dynamic exercise training in foxhounds. II. Analysis of skeletal muscle

The purpose of this study was to determine whether 8-12 wk of endurance training produces biochemical and histochemical adaptations in skeletal muscle in foxhounds. Analyses were performed on samples removed from gastrocnemius, triceps, and semitendinosus muscles of foxhounds before and after a treadmill running program. Biochemical analysis showed that training did not alter the activities of phosphofructokinase, beta-hydroxyacyl-CoA dehydrogenase, succinate dehydrogenase, or total phosphorylase. Histochemical analysis of myofibrillar actomyosin ATPase demonstrated three distinct classes of type II fibers and one type I fiber in the semitendinosus and triceps muscles and two type II and two type I fibers in the gastrocnemius muscle. Fiber type distribution and oxidative and glycolytic potentials, as indicated by nicotinamide adenine dinucleotide tetrazolium reductase or alpha-glycerophosphate dehydrogenase staining intensity, were unaltered by training. Similarly, capillary density, capillary-to-fiber ratios, and capillary area-to-fiber area ratios did not change with training. Thus, unlike humans and other mammals (i.e., rat), these foxhounds did not manifest biochemical or histochemical adaptations in skeletal muscle as the result of endurance training. This is consistent with the results of the study in which endurance training produced a 27% increase in maximal cardiac output and a 4% increase in maximal arteriovenous O2 extraction in foxhounds.     

Fiber type populations and Ca2+-activation properties of single fibers in soleus muscles from SHR and WKY rats

Electrophoretic analyses of muscle proteins in whole musclehomogenates and single muscle fiber segments were used to examine myosin heavy chain (MHC) and myosin light chain 2 (MLC2) isoform composition and fiber type populations in soleus muscles from spontaneously hypertensive rats (SHRs) and their age-matchednormotensive controls [Wistar-Kyoto (WKY) rats], at threestages in the development of high blood pressure (4 wk, 16 wk, and 24 wk of age). Demembranated (chemically skinned with 2% Triton X-100),single fiber preparations were used to determine the maximumCa²⁺-activated force percross-sectional area, calcium sensitivity, and degree of cooperativityof the contractile apparatus andCa²⁺-regulatory system withrespect to Ca²⁺. The results showthat, at all ages examined, 1) SHRsoleus contained a lower proportion of MHCI and MLC2 slow (MLC2s) and ahigher proportion of MHCIIa, MHCIId/x, and MLC2 fast (MLC2f )isoforms than the age-matched controls;2) random dissection of single fibers from SHR and WKY soleus produced four populations of fibers: type I (expressing MHCI), type IIA (expressing MHCIIa), hybrid typeI+IIA (coexpressing MHCI and MHCIIa), and hybrid type IIA+IID (coexpressing MHCIIa and MHCIId/x); and3) single fiber dissection from SHRsoleus yielded a lower proportion of type I fibers, a higher proportionof fast-twitch fibers (types IIA and IIA+IID), and a higher proportionof hybrid fibers (types I+IIA and IIA+IID) than the homologous musclesfrom the age-matched WKY rats. Because the presence of hybrid fibers isviewed as a marker of muscle transformation, these data suggest thatSHR soleus undergoes transformation well into adulthood. Our data showalso that, for a given fiber type, there are no significant differencesbetween SHR and WKY soleus muscles with respect to any of theCa²⁺-activation propertiesexamined. This finding indicates that the lower specific tensionsreported in the literature for SHR soleus muscles are not due tostrain- or hypertension-related differences in the function of thecontractile apparatus or regulatory system.     

Diaphragm capillarity and oxidative capacity during postnatal development.

In the cat diaphragm, fiber capillarity, cross-sectional area, and succinate dehydrogenase (SDH) activity were measured across the first 6 wk of postnatal development. Fibers were classified as type I, IIa, IIb, or IIc on the basis of staining for myofibrillar adenosinetriphosphatase (ATPase). Capillaries were identified in sections stained for ATPase at pH 4.2. Fiber cross-sectional areas and SDH activities were quantified using an image-processing system. During postnatal development, the proportions of type I fibers increased while type II fibers decreased. At birth, all type II fibers were IIc. From the 1st to the 2nd postnatal wk, the proportion of type IIc fibers decreased while the numbers of IIa and IIb increased. Thereafter the proportion of type IIb fibers continued to increase while the number of IIa steadily declined. At birth, capillarity, cross-sectional areas, and SDH activities of type I and II fibers were low compared with other postnatal age groups. Fiber cross-sectional areas increased progressively with age. The number of capillaries surrounding type I and II fibers increased markedly by the 2nd wk and then continued to increase at a slower rate. The number of capillaries per fiber area reached a peak by the 2nd wk and then declined as fiber cross-sectional area increased. Postnatal changes in capillarity depended on fiber type, being greatest in IIb. SDH activities of type I and II fibers were initially low during the first 2 postnatal wk and then peaked by the 3rd wk. After the 6th wk, fiber SDH activities decreased to adult values. Among the type II fibers, IIb showed the greatest change in SDH activity during early postnatal development.     

Lower capillary density but no difference in VEGF expression in obese vs. lean young skeletal muscle in humans.

Obesity is associated with lower skeletal muscle capillarization and lower insulin sensitivity. Vascular endothelial growth factor (VEGF) is important for the maintenance of the skeletal muscle capillaries. To investigate whether VEGF and VEGF receptor [kinase insert domain-containing receptor (KDR) and Flt-1] expression are lower with obesity, vastus lateralis muscle biopsies were obtained from eight obese and eight lean young sedentary men before and 2 h after a 1-h submaximal aerobic exercise bout for the measurement of VEGF, KDR, Flt-1, and skeletal muscle fiber and capillary characteristics. There were no differences in VEGF or VEGF receptor mRNA at rest between lean and obese muscle. Exercise increased VEGF (10-fold), KDR (3-fold), and Flt-1 (5-fold) mRNA independent of group. There were no differences in VEGF, KDR, or Flt-1 protein between groups. Compared with lean skeletal muscle, the number of capillary contacts per fiber was the same, but lower capillary density (CD), greater muscle cross sectional area, and lower capillary-to-fiber area ratio were observed in both type I and II fibers in obese muscle. Multiple linear regression revealed that 49% of the variance in insulin sensitivity (homeostasis model assessment) could be explained by percentage of body fat (35%) and maximal oxygen uptake per kilogram of fat-free mass (14%). Linear regression revealed significant relationships between maximal oxygen uptake and both CD and capillary-to-fiber perimeter exchange. Although differences may exist in CD and capillary-to-fiber area ratio between lean and obese skeletal muscle, the present results provide evidence that VEGF and VEGF receptor expression are not different between lean and obese muscle.